Adenosine deaminase inhibition

Journal Pre-proof Adenosine deaminase inhibition

S. Bagheri, A.A. Saboury, T. Haertlé PII:

S0141-8130(19)34321-1

DOI:

https://doi.org/10.1016/j.ijbiomac.2019.09.078

Reference:

BIOMAC 13323

To appear in:

International Journal of Biological Macromolecules

Received date:

10 June 2019

Revised date:

9 September 2019

Accepted date:

10 September 2019

Please cite this article as: S. Bagheri, A.A. Saboury and T. Haertlé, Adenosine deaminase inhibition, International Journal of Biological Macromolecules(2019), https://doi.org/ 10.1016/j.ijbiomac.2019.09.078

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

© 2019 Published by Elsevier.

Journal Pre-proof Adenosine deaminase inhibition S. Bagheri1,*, A. A. Saboury2,*, T. Haertlé3 1 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

2 Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

of

3 Institut National de la Recherche Agronomique, Nantes, France

ro

Abstract

-p

Adenosine deaminase is a critical enzyme in purine metabolism that regulates intra and extracellular adenosine concentrations by converting it to inosine. Adenosine is an important

re

purine that regulates numerous physiological functions by interacting with its receptors.

lP

Adenosine and consequently adenosine deaminase can have pro or anti-inflammatory effects on

na

tissues depending on how much time has passed from the start of the injury. In addition, an increase in adenosine deaminase activity has been reported for various diseases and the

ur

significant effect of deaminase inhibition on the clinical course of different diseases has been

Jo

reported. However, the use of inhibitors is limited to only a few medical indications. Data on the increase of adenosine deaminase activity in different diseases and the impact of its inhibition in various cases have been collected and are discussed in this review. Overall, the evidence shows that many studies have been done to introduce inhibitors, however, in vivo studies have been much less than in vitro, and often have not been expanded for clinical use. Keywords: Purinergic signaling, Therapeutic strategies, Cancer staging, Disease grading, Diabetes, Cancer

1

Journal Pre-proof Authors Corresponding: Ali Akbar Saboury, Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, Tehran, Iran, Tel: +98-21-66956984, Fax: +98-2166404680, e-mail: [email protected], and Soghra Bagheri, Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, PO Box 67155-1616, Kermanshah,

Iran,

Tel:+98-83-34276473,

Fax:

+98-83-34276471,

Jo

ur

na

lP

re

-p

ro

of

[email protected]

2

e-mal:

Journal Pre-proof 1. Introduction Adenosine deaminase (ADA) is a housekeeping enzyme crucial in purine metabolism. It is a 41 kDa monomeric protein with multiple functions (moonlighting protein), acting as catalyst, costimulator, allosteric modulator, and cell-cell communication molecule [1]. In the field of medicine, ADA’s catalytic activity is in the focus, although other important roles for this enzyme

of

have been revealed more recently [2]. ADA deaminates adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine, respectively. Adenosine and 2'-deoxyadenosine have numerous

ro

physiological functions, and their concentration is strictly controlled [3]. Adenosine exerts its

-p

signaling effects by interaction with G protein-coupled receptors [4]. ADA disrupts the effect of

re

extracellular adenosine by converting it to inosine [5]. ADA also can deaminate adenosine

lP

analogs that are used in chemotherapy and other treatments [6], and can thus alter or compromise their activity and specificity. These activities make ADA a potential therapeutic target for the

na

treatment of various diseases. ADA inhibition has been characterized in a number of studies over

ur

the past 40 years (1979-2019), but no review article on the importance of ADA inhibition has been listed in any of WOS Clarivate Analytics, PubMed, and Scopus databases. This led us to

Jo

write a review article on this subject.

2. Purinergic signaling Extracellular purines (adenosine, ATP, and ADP) and pyrimidines (UDP and UTP) act as important signaling molecules mediating diverse biological processes including smooth muscle contraction, neurotransmission, exocrine and endocrine secretion, the immune response, pain, inflammation, modulation of cardiac function and platelet aggregation through cell surface receptors named purine receptors [7]. The idea of purinergic signaling was in the minds for many

3

Journal Pre-proof years and accepted finally when receptor subtypes for purines and pyrimidines were cloned and characterized [7–10]. There are two classes of purine receptors, P1 (receptors for adenosine) and P2 (receptors for ATP and ADP). The P1 receptors belong to the G-protein coupled receptors and P2 receptors are divided into two families of P2X and P2Y receptors which belong to ligand gated ion channels and G-protein coupled receptors, respectively [7,8]. The pyrimidine receptors (UTP and UDP) belong to the P2 receptor family [7,11–14]. Many studies focused on the

of

pathophysiology and therapeutic potential of these receptors, which led to the use of agonists and

ro

antagonists of different receptors to treat different diseases and disorders including

-p

supraventricular tachycardia [15], Parkinson’s disease [16], thrombosis and stroke [17,18], dry

re

eye [19], chronic cough [20], and inflammatory disorders [16]. Adenosine acts as a signal of tissue damage and inflammatory changes in the proximity of

lP

the immune system [21]. In contrast, 2'-deoxyadenosine acts as a cytotoxic metabolite by

na

perturbing the proliferation and function of B and T cells [22]. Under physiological conditions, the extracellular adenosine concentration is lower than 1 μM (30–200 nM), but can be increased

ur

up to 100 μM in states of inflammation and hypoxia [23]. Extracellular adenosine is mainly

Jo

produced by intracellular ATP breakdown [24] under conditions of low energy charge. AMP originated from ATP degradation is dephosphorylated to adenosine and because of the high Km of ADA (25–150 µM); adenosine is not immediately deaminated to inosine but is accumulated and then exported out of cells via equilibrative nucleoside transporters [25]. On the other hand, extra cellular adenosine can be produced by hydrolysis of adenine nucleotides released to extracellular space in response to cellular stress [26]. Extracellular adenosine can act as a stress signal by interacting with its receptors on the same cell (autocrine signaling) or on the adjacent

4

Journal Pre-proof cells (paracrine signaling) [25]. Intracellular adenosine is synthesized through de novo purine synthesis [27–29] or formed by the breakdown of ATP and other nucleotides [25]. Adenosine receptors are divided into four subtypes, A1, A2A, A2B, and A3, which are all turned on by extracellular adenosine [30]. Playing a role in numerous physiological processes, including sleep, angiogenesis, and modulation of the immune system has made adenosine receptors potential therapeutic targets in various pathological conditions, including sleep

of

disorders, cancers, inflammation, drug addiction, and brain disorders [30–33]. A1 and A3

ro

receptors are coupled to the inhibitory G proteins that resulted in a decrease in intracellular

-p

cAMP, while A2A and A2B cause an increase in cAMP via binding to stimulatory G proteins [34].

re

In addition, A1, A2A and A3 receptors exhibit high affinity for adenosine in human, whereas A2B has a low affinity [29,35]. On the other hand, adenosine receptors have widespread and diverse

lP

distribution in tissues [24] and, depending on receptor distribution, the physiological state of the

na

cells and the extracellular concentration of adenosine, the cell/tissue response to increased adenosine concentration (ADA inhibition) will vary. ATP is released from stressed or damaged

ur

cell, and warns the immune system of imminent danger. ATP exerts a cytotoxic effect by

Jo

inducing the release of pro-inflammatory cytokines of the IL-1 family, and may thus exacerbate tissue damage [36]. The initially high ATP level causes chemotactic and excitatory responses of immune cells. Subsequently, adenosine formed from ATP activates receptors (and downstream signaling) that limit the extent and duration of the inflammatory response and protect cells from injury [37–40]. Adenosine has anti-inflammatory effects in conditions of acute injury, while when sustained beyond the acute injury phase it may have destructive effects on tissue. To prevent this from happening in acute and chronic stages of lung diseases, the use of A2B receptor agonists [41,42] and antagonists [43] was tested in animal models.

5

Journal Pre-proof

3. Adenosine deaminase Adenosine deaminase has two isoenzymes, ADA1 and ADA2 [44]. Mammalian ADA1 has two molecular forms: monomeric ADA1 or small form (41 kDa), and heterooligomeric ADA1cp or large form (>200 kDa), which is a complex between two ADA1 subunits and the non-enzymatic homodimeric glycoprotein CD26, a T cell activation marker (Fig. 1) [45,46]. ADA1 is also

of

associated with A1, A2A, and A2B adenosine receptors (Fig. 2) [1,47–52]. ADA1 and ADA1cp

ro

isoenzymes account for up to 90% of total ADA activity. ADA2 contributes little to the ADA

-p

activity of liver and spleen but considerably to the ADA activity of serum [46]. Unlike ADA1,

re

ADA2 is not ubiquitous and coexists with ADA1 only in monocytes-macrophages. Monocytesmacrophages exert a critical function in immune defense and their ADA2 concentration increases

lP

in response to an infection by intracellular microorganisms [44].

na

In addition to ADA1 that can be connected to the surface of the cells (ecto-ADA), ADA2 is also connected to the surface of different cells via proteoglycans and adenosine receptors [53].

ur

On the other hand, in addition to the presence of these isoenzymes in the cytosolic and ecto-

Jo

forms, they can also be secreted in a variety of conditions, for example, ADA2 is secreted when monocytes differentiate into macrophages [53] or ADA1 and 2 are secreted to serum and other fluids in various diseases [54–60] (refer to Table 1).

4. Role of ADA in adenosine signaling Ecto-ADA plays an extra-enzymatic role in addition to deamination of extracellular adenosine that leads to reduce the stimulation of adenosine receptors. By binding to CD26 and adenosine receptors, ADA acts as immunomodulatory and allosteric regulator. By simultaneous binding to

6

Journal Pre-proof CD26 and adenosine receptors on different cells, ecto-ADA mediates cell to cell contacts [47,61–65]. It is possible, that this bridging function of ecto-ADA facilitates intercellular signal transduction important for tumor development [66]. Adenosine can have different effects depending on target tissue and time course [67,68]. The different physiological effects of adenosine are partly due to the fact that different adenosine receptors may have opposing functions [67] so that the activation of one may elicit a protective

of

reaction and of another a pathological response. For the same reason ADA can have pro- or anti-

ro

inflammatory effects depending on the immune status.

-p

ADA is expressed in all human tissues, but at higher concentrations in lymphoid cells, where

re

it plays an important role for their maturation and differentiation [46]. Various mutations in the ADA gene have been detected in patients with lymphopenia. ADA deficiency accounts for 10-

lP

20% of human severe combined immunodeficiency (SCID) [69]. Increased extracellular

na

adenosine inhibits the activity of the immune cells by stimulation of adenosine receptors [70] and can result in apoptosis of lymphoid cells [71]. On the other hand, increased ADA activity was

ur

detected in lymphoid malignancies [72]. These findings prompted attempts to use ADA

Jo

inhibitors for the treatment of lymphoid malignancies [73–81]. In the following section, we focus attention on the pathology of increased ADA activity and concomitant decreased adenosine concentrations. For the pathology of ADA defects and resulting from it the accumulation of cytotoxic levels of (deoxy) adenosine and dATP, the reader is referred to [82].

5. Increase of ADA activity in different diseases An increase in ADA activity results in inflammation and tissue injury [83]. High ADA activity occurs in various diseases and disorders including different cancers (Table 1), in addition, its

7

Journal Pre-proof association with disease staging [46,84–94] and, cancer staging both, in serum [95–100] and in cancerous tissues [98,101–104] has been reported. This suggests ADA activity as an effective biomarker to diagnose disease and monitor the therapeutic success. Besides to ADA activity, the proportion of isoenzyme activities are also dependent on the immune status of the patient [94,105–109]. For instance, there is evidence for a significant increase of serum ADA isoenzymes in patients with AIDS and HIV-1 antibody-positive, which is higher than in HIV-1

of

antibody-negative individuals. On the other hand, serum ADA2 activity was significantly higher

ro

in patients with AIDS than in HIV-1 antibody-positive individuals. In fact, the increase of serum

-p

ADA isoenzymes was correlated with the clinical status of the patients [46].

re

A decrease in ADA activity and its association with the progression of the disease has been reported in some cancers (Table 2) suggesting a mechanism that neutralizes the increased rate of

na

lP

purine and DNA metabolism in cancer cells [110].

6. Therapeutic strategies for the use of ADA inhibitors

ur

The substrate of ADA (adenosine) is a regulator of inflammation and tissue injury [111,112], and

Jo

the severity of inflammation therefore is correlated with adenosine-deaminase activity [113]. The inhibition of adenosine deamination leads to the accumulation of adenosine in the inflammation site and to activation of purinergic responses [114]. On the other hand, inhibition of ADA can lead to reduce free radicals production, which is a side effect of many anticancer medications [115]. Furthermore, adenosine analogs that are used for chemotherapy of cancers and other diseases can be deaminated and inactivated by ADA [116,117]. In addition, ADA inhibition prevents binding of enzyme with T cell activation marker (CD26) and adenosine receptors [118]. These advantages potentiate ADA inhibition as a suitable anti-inflammatory treatment [113] and

8

Journal Pre-proof consequently many studies were axed on ADA inhibitors in order to include them as potential therapeutic agents (Tables 3 and 4). Tables 3 and 4 focus on the inhibitors that have been studied after 2001. To study the used inhibitors before the mentioned time, one can refer to [119]. Despite many in vitro studies, the number of in vivo studies is limited (Tables 3 and 4). However, these studies have shown the significant effect of enzyme inhibition on diseases control, which will be briefly discussed in the following. Hairy cell leukemia is one of the

of

diseases that has been studied using ADA inhibitors for treatment and has reached the clinical

ro

use stage of the inhibitors. ADA inhibitors inhibit the proliferation of leukemia and lymphoma

-p

cells, and use of 2ˊ-deoxyadenosine and its analogs enhance inhibitory effects of ADA inhibitors

re

[120,121]. Studies have shown that pentostatin (a strong ADA inhibitor) and cladribine (the chlorinated derivative of deoxyadenosine) are very efficient in hairy cell leukemia treatment

lP

[81,121].

na

Another area where enzyme inhibition has been considered is the treatment of brain-related disorders that adenosine and its metabolism play a prominent role. Adenosine promotes sleep

ur

whereas opioids disrupt it [122–125]. Opioids reduce adenosine levels in the brain [126]. They

Jo

are excellent pain reducers, but because they disrupt sleep also enhance pain perception [127,128], and consequently require higher dosing which however is unwanted [129]. Coadministration of ADA inhibitors and opioids prevents the decrease in adenosine levels caused by morphine alone [126]. Other promising studies include investigating the effect of ADA inhibition in the treatment of nervous system tumors. Inhibition of ADA has a significant effect on the apoptosis of chemotherapy-resistant astrocytoma cell lines [130,131], and human neuroblastoma cell lines, SH-SY5Y and LAN5, undergo apoptotic death after treatment with deoxycoformycin in combination with deoxyadenosine. This further indicates that perturbation

9

Journal Pre-proof of purine metabolism may be a new therapeutic approach to cure nervous system tumors [132,133]. ADA inhibition decreases tumor size and tumor growth in mouse models of breast cancer and human breast cancer cells as well [134]. Another area of interest to researchers is the use of inhibitors in the treatment of gastrointestinal inflammatory diseases. ADA inhibition reduces inflammation in animal models of colitis [135,136] and prevents tissue injury and inflammation in toxin A-induced enteritis in

of

mice [137]. In addition, local inhibition of intestinal ADA increased the efficacy of orally

ro

delivered drugs used for AIDS and anti-HIV therapy [138,139].

-p

The effects of inhibitors on the other pathological conditions such as sepsis and psoriasis

re

have also been reported. Propylthiouracil, an antithyroid drug which has beneficial effects on psoriatic lesions [140], and other common drugs that are used to treat psoriasis patients bring

lP

down the pathologically elevated ADA activity in skin and plasma of treated patients [141].

[142–145].

na

Furthermore, ADA inhibitors reduce microvascular dysfunction and enhance survival in sepsis

ur

EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), an ADA inhibitor, has a similar effect as

Jo

knocking-down the ADA gene, it increases intracellular adenosine level resulting in apoptosis of malignant pleural mesothelioma cells. Malignant pleural mesothelioma is an invasive malignant tumor against which no effective treatment has been provided so far [146]. Although vast number of natural and synthetic ADA inhibitors have been studied only a few inhibitors are used in the clinic [114]. In fact, high levels of adenosine that are produced in the presence of strong ADA inhibitors can be toxic to cells and promote their apoptosis [147] for instance pentostatin can induce immune deficiency [148], but the use of less-potent inhibitors such as naringin can prevent this undesirable effect [117].

10

Journal Pre-proof Several studies suggest natural compounds such as tomato juice, Urtica dioica, endophytes metabolites, Syzygium cumini and Allium sativum,or commonly used medications such as methotrexate and organogermanium compound to inhibit ADA. A prospective cohort study and several epidemiological studies have shown that normal consumption of tomato products can have a protective effect against prostate cancer [149–152]. The beneficial effect has been attributed primarily to a potent antioxidant property of tomato lycopen [151,153–156]. However,

of

it has been shown that tomato juice significantly inhibits ADA activity in prostate cancer tissues

ro

[157]. Urtica dioica (stinging nettle) the most popular herb for cancer therapy that has anti-

-p

proliferative activity in human prostatic epithelial cells [158], can greatly inhibit ADA activity in

re

human prostate cancer tissues [159]. Recently a strong uncompetitive inhibitor of ADA activity was isolated from the endophytic fungus Aspergillus niger [6] indicating that endophytes

lP

(endosymbionts in plant tissues) may be a promising sources of novel ADA inhibitors and other

na

bioactive metabolites.

Syzygium cumini (Jambolan, Java plum) is a traditional plant medicine that is widely used by

ur

traditional practitioners to treat diabetes [160]. Seed extracts of Syzygium cumini improve the

Jo

level of insulin, hyperglycemia, hyperlipidemia, oxidative stress, kidney and liver dysfunction in animal models [161] and they inhibit ADA activity in human and animal models [160,162–165]. Allium sativum (garlic) is one of the most popular traditional plant medicine worldwide that is used to treat many diseases [166]. Garlic has antihyperglycemic and lipid-lowering effects, inhibits ADA activity in vitro and in patients with type-2 diabetes mellitus and obesity [166– 171]. Some conventional drugs also affect the activity of ADA (Tables 3 and 4). Methotrexate, used to treat rheumatoid arthritis, various cancers, and autoimmune diseases [172], induces

11

Journal Pre-proof adenosine release in inflamed sites by inhibition of ADA [173–176]. The organogermanium compound Ge-132 inhibits ADA and interacts with nucleic acid components [177]. It also has antitumor [178], anti-inflammatory [179], immunostimulatory [180,181], and painkiller activities and exhibits extremely low level toxicity in animals and human [177]. Although existing reports indicate a significant effect of enzyme inhibition on the treatment process in cell culture, animal models, and patients, these investigations often have not been

ro

of

expanded and led to introduce a medication.

-p

11. Conclusion

re

Despite numerous studies that have shown enzyme inhibition as an effective treatment strategy for various diseases, and despite many inhibitors that have been studied and proposed, ADA

lP

inhibition seems to have been still underestimated in the field of treatments of different

na

pathologies. In fact, apart from pentostatin, cladribine, and fludarabine, which are used against leukemia and lymphoma, only dipyridamole, used for promotion of vasodilatation and inhibiting

ur

platelet aggregation, is used in clinic, and the inhibition of ADA, and consequently the use of its

Jo

inhibitors has not been taken into account for the treatment of other diseases in clinic.

Acknowledgement We would like to thank Professor Bernhard Erni, Department of Chemistry and Biochemistry, University of Bern, Switzerland, for his editing and nice comments.

12

Journal Pre-proof References [1]

E. Moreno, J. Canet, E. Gracia, C. Lluís, J. Mallol, E.I. Canela, A. Cortés, V. Casadó, Molecular evidence of adenosine deaminase linking adenosine A2Areceptor and CD26 proteins, Front. Pharmacol. 9 (2018) 106. doi:10.3389/fphar.2018.00106.

[2]

A. Cortés, E. Gracia, E. Moreno, J. Mallol, C. Lluís, E.I. Canela, V. Casadó, Moonlighting

of

Adenosine Deaminase: A Target Protein for Drug Development, Med. Res. Rev. 35

J. Park, R.S. Gupta, Adenosine Metabolism, Adenosine Kinase, and Evolution, in:

-p

[3]

ro

(2015) 85–125. doi:10.1002/med.21324.

re

Adenosine, Springer New York, New York, NY, 2013: pp. 23–54. doi:10.1007/978-1-

[4]

lP

4614-3903-5_2.

B.B. Fredholm, A.P. IJzerman, K.A. Jacobson, J. Linden, C.E. Muller, International

na

Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of

ur

Adenosine Receptors--An Update, Pharmacol. Rev. 63 (2011) 1–34.

[5]

Jo

doi:10.1124/pr.110.003285.

H. Liu, Y. Xia, Beneficial and detrimental role of adenosine signaling in diseases and therapy, J. Appl. Physiol. 119 (2015) 1173–1182. doi:10.1152/japplphysiol.00350.2015.

[6]

X. guo Zhang, J. wen Liu, P. Tang, Z. yu Liu, G.J. Guo, Q.Y. Sun, J. jun Yin, Identification of a New Uncompetitive Inhibitor of Adenosine Deaminase from Endophyte Aspergillus niger sp., Curr. Microbiol. 75 (2018) 565–573. doi:10.1007/s00284-017-14184.

[7]

V. Ralevic, G. Burnstock, Receptors for purines and pyrimidines., Pharmacol. Rev. 50 13

Journal Pre-proof (1998) 413–92. [8]

B.B. Fredholm, M.P. Abbracchio, G. Burnstock, J.W. Daly, T.K. Harden, K.A. Jacobson, P. Leff, M. Williams, Nomenclature and classification of purinoceptors., Pharmacol. Rev. 46 (1994) 143–56.

[9]

L. Antonioli, M. Fornai, R. Colucci, N. Ghisu, M. Tuccori, M. Del Tacca, C. Blandizzi,

of

Regulation of enteric functions by adenosine: Pathophysiological and pharmacological

ro

implications, Pharmacol. Ther. (2008). doi:10.1016/j.pharmthera.2008.08.010.

-p

[10] L. Antonioli, R. Colucci, C. Pellegrini, G. Giustarini, M. Tuccori, C. Blandizzi, M. Fornai,

re

The role of purinergic pathways in the pathophysiology of gut diseases: Pharmacological modulation and potential therapeutic applications, Pharmacol. Ther. 139 (2013) 157–188.

lP

doi:10.1016/j.pharmthera.2013.04.002.

na

[11] A.C.A. Moreira-Souza, Y. Marinho, G. Correa, G.F. Santoro, C.M.L.M. Coutinho, R.C.

ur

Vommaro, R. Coutinho-Silva, Pyrimidinergic receptor activation controls Toxoplasma gondii infection in macrophages, PLoS One. 10 (2015) e0133502.

Jo

doi:10.1371/journal.pone.0133502. [12] I. von Kügelgen, Pharmacology of P2Y receptors, Brain Res. Bull. 151 (2019) 12–24. doi:10.1016/j.brainresbull.2019.03.010. [13] M. Rafehi, C.E. Müller, Tools and drugs for uracil nucleotide-activated P2Y receptors, Pharmacol. Ther. 190 (2018) 24–80. doi:10.1016/j.pharmthera.2018.04.002. [14] R. Lu, Z. Zhang, C. Jiang, Recent progress on the discovery of P2Y14 receptor antagonists, Eur. J. Med. Chem. 175 (2019) 34–39. doi:10.1016/j.ejmech.2019.04.068. 14

Journal Pre-proof [15] S. Sachdeva, M. Gupta, Adenosine and its receptors as therapeutic targets: An overview, Saudi Pharm. J. 21 (2013) 245–253. doi:10.1016/j.jsps.2012.05.011. [16] G. Burnstock, Purinergic Signalling: Therapeutic Developments, Front. Pharmacol. 8 (2017) 661. doi:10.3389/fphar.2017.00661. [17] N. Sarafoff, R.A. Byrne, D. Sibbing, Clinical use of clopidogrel., Curr. Pharm. Des. 18

of

(2012) 5224–39.

ro

[18] F. Rollini, F. Franchi, D.J. Angiolillo, Drug-Drug Interactions When Switching Between

re

130–132. doi:10.1016/j.jcin.2016.11.021.

-p

Intravenous and Oral P2Y 12 Receptor Inhibitors, JACC Cardiovasc. Interv. 10 (2017)

lP

[19] O.C.F. Lau, C. Samarawickrama, S.E. Skalicky, P2Y2 receptor agonists for the treatment of dry eye disease: a review., Clin. Ophthalmol. 8 (2014) 327–34.

na

doi:10.2147/OPTH.S39699.

ur

[20] R. Abdulqawi, R. Dockry, K. Holt, G. Layton, B.G. McCarthy, A.P. Ford, J.A. Smith,

Jo

P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, doubleblind, placebo-controlled phase 2 study, Lancet. 385 (2015) 1198–1205. doi:10.1016/S0140-6736(14)61255-1. [21] V. Kumar, A. Sharma, Adenosine: An endogenous modulator of innate immune system with therapeutic potential, Eur. J. Pharmacol. 616 (2009) 7–15. doi:10.1016/j.ejphar.2009.05.005. [22] T. Sato, T.-S. Chan, Deoxyadenosine blockade of G0 to G1 transition in lymphocytes: Possible involvement of protein kinases, J. Cell. Physiol. 166 (1996) 288–295. 15

Journal Pre-proof doi:10.1002/(SICI)1097-4652(199602)166:2<288::AID-JCP6>3.0.CO;2-L. [23] G. Haskó, B.N. Cronstein, Adenosine: an endogenous regulator of innate immunity., Trends Immunol. 25 (2004) 33–9. [24] J.F. Chen, H.K. Eltzschig, B.B. Fredholm, Adenosine receptors as drug targets-what are the challenges?, Nat. Rev. Drug Discov. 12 (2013) 265–286. doi:10.1038/nrd3955.

of

[25] M. Camici, M. Garcia-Gil, M. Tozzi, M. Camici, M. Garcia-Gil, M.G. Tozzi, The Inside

ro

Story of Adenosine, Int. J. Mol. Sci. 19 (2018) 784. doi:10.3390/ijms19030784.

-p

[26] H.K. Eltzschig, Adenosine: An old drug newly discovered, Anesthesiology. (2009).

re

doi:10.1097/ALN.0b013e3181b060f2.

na

Biochem. 140 (1994) 1–22.

lP

[27] T.W. Traut, Physiological concentrations of purines and pyrimidines., Mol. Cell.

[28] P.L. Ipata, R. Pesi, Nucleoside recycling in the brain and the nucleosidome: a complex

ur

metabolic and molecular cross-talk between the extracellular nucleotide cascade system

Jo

and the intracellular nucleoside salvage, Metabolomics. 12 (2016) 22. doi:10.1007/s11306-015-0931-3. [29] J. Layland, D. Carrick, M. Lee, K. Oldroyd, C. Berry, Adenosine: Physiology, pharmacology, and clinical applications, JACC Cardiovasc. Interv. (2014). doi:10.1016/j.jcin.2014.02.009. [30] B. Carpenter, G. Lebon, Human Adenosine A2A Receptor: Molecular Mechanism of Ligand Binding and Activation., Front. Pharmacol. 8 (2017) 898. doi:10.3389/fphar.2017.00898. 16

Journal Pre-proof [31] S. Menzel, N. Schwarz, F. Haag, F. Koch-Nolte, Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity, Front. Pharmacol. 9 (2018) 266. doi:10.3389/fphar.2018.00266. [32] A.M. Sebastião, N. Rei, J.A. Ribeiro, Amyotrophic Lateral Sclerosis (ALS) and Adenosine Receptors, Front. Pharmacol. 9 (2018) 267. doi:10.3389/fphar.2018.00267.

of

[33] S. Gessi, S. Bencivenni, E. Battistello, F. Vincenzi, V. Colotta, D. Catarzi, F. Varano, S.

ro

Merighi, P.A. Borea, K. Varani, Inhibition of A2A Adenosine Receptor Signaling in

-p

Cancer Cells Proliferation by the Novel Antagonist TP455, Front. Pharmacol. 8 (2017)

re

888. doi:10.3389/fphar.2017.00888.

[34] M. Cattaneo, R. Schulz, S. Nylander, Adenosine-mediated effects of ticagrelor: Evidence

lP

and potential clinical relevance, J. Am. Coll. Cardiol. (2014).

na

doi:10.1016/j.jacc.2014.03.031.

ur

[35] F. Ciruela, C. Albergaria, A. Soriano, L. Cuffí, L. Carbonell, S. Sánchez, J. Gandía, V. Fernández-Dueñas, Adenosine receptors interacting proteins (ARIPs): Behind the biology

Jo

of adenosine signaling, Biochim. Biophys. Acta - Biomembr. (2010). doi:10.1016/j.bbamem.2009.10.016. [36] F. Virgilio, Purinergic signalling in the immune system. A brief update, Purinergic Signal. 3 (2007) 1–3. doi:10.1007/s11302-006-9048-5. [37] Y. Zhou, D.J. Schneider, E. Morschl, L. Song, M. Pedroza, H. Karmouty-Quintana, T. Le, C.-X. Sun, M.R. Blackburn, Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury, J. Immunol. 186 (2011) 1097–1106.

17

Journal Pre-proof doi:10.4049/jimmunol.1002907. [38] C. Cekic, J. Linden, Purinergic regulation of the immune system, Nat. Rev. Immunol. 16 (2016) 177–192. doi:10.1038/nri.2016.4. [39] J. Lee, Ö. Yilmaz, Unfolding Role of a Danger Molecule Adenosine Signaling in Modulation of Microbial Infection and Host Cell Response, Int. J. Mol. Sci. 19 (2018)

of

199. doi:10.3390/ijms19010199.

ro

[40] H. Karmouty-Quintana, Y. Xia, M.R. Blackburn, Adenosine signaling during acute and

-p

chronic disease states, J. Mol. Med. 91 (2013) 173–181. doi:10.1007/s00109-013-0997-1.

re

[41] T. Eckle, M. Faigle, A. Grenz, S. Laucher, L.F. Thompson, H.K. Eltzschig, A2B

lP

adenosine receptor dampens hypoxia-induced vascular leak, Blood. 111 (2008) 2024–

na

2035. doi:10.1182/blood-2007-10-117044. [42] T. Eckle, A. Grenz, S. Laucher, H.K. Eltzschig, A2B adenosine receptor signaling

ur

attenuates acute lung injury by enhancing alveolar fluid clearance in mice, J. Clin. Invest.

Jo

118 (2008) 3301–3315. doi:10.1172/JCI34203. [43] C.X. Sun, H. Zhong, A. Mohsenin, E. Morschl, J.L. Chunn, J.G. Molina, L. Belardinelli, D. Zeng, M.R. Blackburn, Role of A2Badenosine receptor signaling in adenosinedependent pulmonary inflammation and injury, J. Clin. Invest. 116 (2006) 2173–2182. doi:10.1172/JCI27303. [44] C. Gakis, Adenosine deaminase (ADA) isoenzymes ADA1 and ADA2: Diagnostic and biological role, Eur. Respir. J. 9 (1996) 632–633. doi:10.1183/09031936.96.09040632. [45] R. Franco, V. Casadó, F. Ciruela, C. Saura, J. Mallol, E.I. Canela, C. Lluis, Cell surface 18

Journal Pre-proof adenosine deaminase: much more than an ectoenzyme., Prog. Neurobiol. 52 (1997) 283– 94. [46] I. Tsuboi, K. Sagawa, S. Shichijo, M.M. Yokoyama, D.W. Ou, M.D. Wiederhold, Adenosine deaminase isoenzyme levels in patients with human T-cell lymphotropic virus type 1 and human immunodeficiency virus type 1 infections., Clin. Diagn. Lab. Immunol.

of

2 (1995) 626–630.

ro

[47] F. Ciruela, C. Saura, E.I. Canela, J. Mallol, C. Lluis, R. Franco, Adenosine deaminase

-p

affects ligand-induced signalling by interacting with cell surface adenosine receptors,

re

FEBS Lett. 380 (1996) 219–223. doi:10.1016/0014-5793(96)00023-3. [48] C. Herrera, V. Casadó, F. Ciruela, P. Schofield, J. Mallol, C. Lluis, R. Franco, Adenosine

lP

A 2B Receptors Behave as an Alternative Anchoring Protein for Cell Surface Adenosine

na

Deaminase in Lymphocytes and Cultured Cells, Mol. Pharmacol. 59 (2001) 127–134.

ur

doi:10.1055/s-2007-965439.

[49] R.M. Arin, A.I. Vallejo, Y. Rueda, O. Fresnedo, B. Ochoa, The A2B adenosine receptor

Jo

colocalizes with adenosine deaminase in resting parietal cells from gastric mucosa., Biochemistry. (Mosc). 80 (2015) 120–5. doi:10.1134/S0006297915010149. [50] R.M. Arin, A.I. Vallejo, Y. Rueda, O. Fresnedo, B. Ochoa, Expression of adenosine A2Breceptor and adenosine deaminase in rabbit gastric mucosa ECL cells, Molecules. 22 (2017) 625. doi:10.3390/molecules22040625. [51] C. Saura, F. Ciruela, V. Casado, E.I. Canela, J. Mallol, C. Lluis, R. Franco, V. Casadó, Adenosine deaminase interacts with A1 adenosine receptors in pig brain cortical

19

Journal Pre-proof membranes, J. Neurochem. 66 (1996) 1675–1682. [52] L. Antonioli, M. Fornai, O. Awwad, G. Giustarini, C. Pellegrini, M. Tuccori, V. Caputi, M. Qesari, I. Castagliuolo, P. Brun, M.C. Giron, C. Scarpignato, C. Blandizzi, R. Colucci, Role of the A2B receptor-adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats, Br. J. Pharmacol. (2014). doi:10.1111/bph.12539.

of

[53] A. V. Zavialov, E. Gracia, N. Glaichenhaus, R. Franco, A. V. Zavialov, G. Lauvau,

ro

Human adenosine deaminase 2 induces differentiation of monocytes into macrophages

-p

and stimulates proliferation of T helper cells and macrophages, J. Leukoc. Biol. 88 (2010)

re

279–290. doi:10.1189/jlb.1109764.

[54] S. Iwaki-Egawa, T. Yamamoto, Y. Watanabe, Human plasma adenosine deaminase 2 is

na

doi:10.1515/BC.2006.042.

lP

secreted by activated monocytes, Biol. Chem. 387 (2006) 319–321.

ur

[55] J.P. Ungerer, S.M. Grobler, Molecular forms of adenosine deaminase in pleural effusions.,

Jo

Enzyme. 40 (1988) 7–13.

[56] S. Yurt, C. Küçükergin, B.A. Yigitbas, Ş. Seçkin, H.C. Tigin, A.F. Koşar, Diagnostic utility of serum and pleural levels of adenosine deaminase 1–2, and interferon-γ in the diagnosis of pleural tuberculosis, Multidiscip. Respir. Med. 9 (2014) 12. doi:10.1186/2049-6958-9-12. [57] B. Kutryb-Zajac, L. Mateuszuk, P. Zukowska, A. Jasztal, M.A. Zabielska, M. Toczek, P. Jablonska, A. Zakrzewska, B. Sitek, J. Rogowski, R. Lango, E.M. Slominska, S. Chlopicki, R.T. Smolenski, Increased activity of vascular adenosine deaminase in

20

Journal Pre-proof atherosclerosis and therapeutic potential of its inhibition, Cardiovasc. Res. 112 (2016) 590–605. doi:10.1093/cvr/cvw203. [58] E. Richard, F.X. Arredondo-Vega, I. Santisteban, S.J. Kelly, D.D. Patel, M.S. Hershfield, The binding site of human adenosine deaminase for CD26/dipeptidyl peptidase IV: The Arg142Gln mutation impairs binding to CD26 but does not cause immune deficiency, J.

of

Exp. Med. (2000). doi:10.1084/jem.192.9.1223.

ro

[59] P. Correia-de-Sá, S. Adães, M.A. Timóteo, C. Vieira, T. Magalhães-Cardoso, C.

-p

Nascimento, M. Duarte-Araújo, Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: On the role of secreted adenosine deaminase, Auton. Neurosci.

re

Basic Clin. (2006). doi:10.1016/j.autneu.2006.02.004.

lP

[60] C. Vieira, M.T. Magalhães-Cardoso, F. Ferreirinha, I. Silva, A.S. Dias, J. Pelletier, J.

na

Sévigny, P. Correia-De-Sá, Feed-forward inhibition of cd73 and upregulation of adenosine deaminase contribute to the loss of adenosine neuromodulation in

ur

postinflammatory ileitis, Mediators Inflamm. 2014 (2014). doi:10.1155/2014/254640.

Jo

[61] T. Hashikawa, S.W. Hooker, J.G. Maj, C.J. Knott-Craig, M. Takedachi, S. Murakami, L.F. Thompson, Regulation of adenosine receptor engagement by ecto-adenosine deaminase., FASEB J. 18 (2004) 131–133. doi:10.1096/fj.03-0011fje. [62] D.D. Jeanfavre, J.R. Woska, C.A. Pargellis, C.A. Kennedy, J. Prendergast, C. Stearns, P.L. Reilly, R.W. Barton, B.J. Bormann, Effect of deoxycoformycin and Val-boroPro on the associated catalytic activities of lymphocyte CD26 and ecto-adenosine deaminase, Biochem. Pharmacol. 52 (1996) 1757–1765. doi:10.1016/S0006-2952(96)00597-7.

21

Journal Pre-proof [63] C. Lluis, R. Franco, O. Cordero, L.F. Thompson, R. Resta, Ecto-ADA in the development of the immune system, Immunol. Today. 19 (1998) 533–534. doi:10.1016/S01675699(98)01331-0. [64] R. Pacheco, J.M. Martinez-Navio, M. Lejeune, N. Climent, H. Oliva, J.M. Gatell, T. Gallart, J. Mallol, C. Lluis, R. Franco, CD26, adenosine deaminase, and adenosine

of

receptors mediate costimulatory signals in the immunological synapse, Proc. Natl. Acad.

ro

Sci. 102 (2005) 9583–9588. doi:10.1073/pnas.0501050102.

-p

[65] M. Romanowska, M. Ostrowska, M.A. Komoszyński, Adenosine ecto-deaminase (ecto-

doi:10.1016/j.brainres.2007.04.037.

re

ADA) from porcine cerebral cortex synaptic membrane, Brain Res. 1156 (2007) 1–8.

lP

[66] F. Gloria-Bottini, P. Saccucci, M. Ammendola, A. Neri, A. Magrini, E. Bottini, Genetic

na

variability within Adenosine Deaminase gene and uterine leiomyomas, Eur. J. Obstet.

ur

Gynecol. Reprod. Biol. 199 (2016) 108–109. doi:10.1016/j.ejogrb.2016.02.002. [67] B.B. Fredholm, Adenosine, an endogenous distress signal, modulates tissue damage and

Jo

repair, Cell Death Differ. 14 (2007) 1315–1323. doi:10.1038/sj.cdd.4402132. [68] A. Van Linden, H.K. Eltzschig, Role of pulmonary adenosine during hypoxia: extracellular generation, signaling and metabolism by surface adenosine deaminase/CD26, Expert Opin. Biol. Ther. 7 (2007) 1437–1447. doi:10.1517/14712598.7.9.1437. [69] K.L. Bradford, F.A. Moretti, D.A. Carbonaro-Sarracino, H.B. Gaspar, D.B. Kohn, Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations, J. Clin. Immunol. 37 (2017) 626–

22

Journal Pre-proof 637. doi:10.1007/s10875-017-0433-3. [70] A. Ohta, E. Gorelik, S.J. Prasad, F. Ronchese, D. Lukashev, M.K.K. Wong, X. Huang, S. Caldwell, K. Liu, P. Smith, J.-F. Chen, E.K. Jackson, S. Apasov, S. Abrams, M. Sitkovsky, A2A adenosine receptor protects tumors from antitumor T cells, Proc. Natl. Acad. Sci. 103 (2006) 13132–13137. doi:10.1073/pnas.0605251103.

of

[71] L.F. Thompson, J.G. Vaughn, A.B. Laurent, M.R. Blackburn, C.J. Van De Wiele,

ro

Mechanisms of apoptosis in developing thymocytes as revealed by adenosine deaminase-

-p

deficient fetal thymic organ cultures., Biochem. Pharmacol. 66 (2003) 1595–9.

re

[72] M.K. Riscoe, M.C. Brouns, J.H. Fitchen, Purine metabolism as a target for leukemia

lP

chemotherapy, Blood Rev. 3 (1989) 162–173. doi:10.1016/0268-960X(89)90013-1. [73] M.R. Grever, C.A. Doan, E.H. Kraut, Pentostatin in the treatment of hairy-cell leukemia.,

na

Best Pract. Res. Clin. Haematol. 16 (2003) 91–9.

ur

[74] D. Greiner, E.A. Olsen, G. Petroni, Pentostatin (2’-deoxycoformycin) in the treatment of

Jo

cutaneous T-cell lymphoma, J. Am. Acad. Dermatol. 36 (1997) 950–955. doi:10.1016/S0190-9622(97)80279-4. [75] A.-M. Tsimberidou, F. Giles, M. Duvic, L. Fayad, R. Kurzrock, Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an M.D. Anderson Cancer Center series., Cancer. 100 (2004) 342–9. doi:10.1002/cncr.11899. [76] A. von Rohr, S.F.H. Schmitz, A. Tichelli, U. Hess, D. Piguet, M. Wernli, N. Frickhofen, G. Konwalinka, G. Zulian, M. Ghielmini, B. Rufener, C. Racine, M.F. Fey, T. Cerny, D. Betticher, A. Tobler, Treatment of hairy cell leukemia with cladribine (223

Journal Pre-proof chlorodeoxyadenosine) by subcutaneous bolus injection: A phase II study, Ann. Oncol. 13 (2002) 1641–1649. doi:10.1093/annonc/mdf272. [77] C. Sauter, N. Lamanna, M.A. Weiss, Pentostatin in chronic lymphocytic leukemia, Expert Opin Drug Metab Toxicol. 4 (2008) 1217–1222. doi:10.1517/17425255.4.9.1217. [78] N.E. Kay, S.M. Geyer, T.G. Call, T.D. Shanafelt, C.S. Zent, D.F. Jelinek, R. Tschumper,

of

N.D. Bone, G.W. Dewald, T.S. Lin, N.A. Heerema, L. Smith, M.R. Grever, J.C. Byrd,

ro

Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab

-p

shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia, Blood. 109 (2007) 405–411. doi:10.1182/blood-2006-

re

07-033274.

lP

[79] A.D. Ho, M. Hensel, Pentostatin for the Treatment of Indolent Lymphoproliferative

na

Disorders, Semin. Hematol. 43 (2006) S2–S10. doi:10.1053/j.seminhematol.2005.12.005.

ur

[80] R.O. Dillman, Pentostatin (Nipent®) in the treatment of chronic lymphocyte leukemia and hairy cell leukemia, Expert Rev. Anticancer Ther. 4 (2004) 27–36.

Jo

doi:10.1586/14787210.4.1.27.

[81] L. Piro, C. Carrera, D. Carson, E. Buetler, Lasting remissions in hairy cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine, N. Engl. J. Med. 322 (1990) 1117–21. doi:10.1056/NEJM199004193221605. [82] A.M. Flinn, A.R. Gennery, Adenosine deaminase deficiency: a review, Orphanet J. Rare Dis. 13 (2018) 65. doi:10.1186/s13023-018-0807-5. [83] A.S. da Silva, J.M. Santurio, L.F. Roza, N.B. Bottari, G.M. Galli, V.M. Morsch, M.R.C. 24

Journal Pre-proof Schetinger, M.D. Baldissera, L.M. Stefani, W.M. Radavelli, T. Tomasi, M.M. Boiago, Aflatoxins produced by Aspergillus parasiticus present in the diet of quails increase the activities of cholinesterase and adenosine deaminase, Microb. Pathog. 107 (2017) 309– 312. doi:10.1016/j.micpath.2017.03.041. [84] M. Ibiş, S. Köklü, F.M. Yilmaz, Ö. Başar, G. Yilmaz, O. Yüksel, E. Yildirim, Z.A.

of

Öztürk, Serum adenosine deaminase levels in pancreatic diseases, Pancreatology. 7 (2007)

ro

526–530. doi:10.1159/000108970.

-p

[85] S. Chiba, M. Saitoh, M. Kashiwagi, N. Kobayashi, H. Matsumoto, Isozyme Analysis of the High Serum Adenosine Deaminase Activity in Patients with Myasthenia Gravis.,

re

Intern. Med. 34 (1995) 81–84. doi:10.2169/internalmedicine.34.81.

lP

[86] L. Oliveira, A. Correia, A. Cristina Costa, S. Guerra-Gomes, F. Ferreirinha, M.T.

na

Magalhães-Cardoso, M. Vilanova, P. Correia-de-Sá, Deficits in Endogenous Adenosine Formation by Ecto-5′-Nucleotidase/CD73 Impair Neuromuscular Transmission and

ur

Immune Competence in Experimental Autoimmune Myasthenia Gravis, Mediators

Jo

Inflamm. 2015 (2015) 1–16. doi:10.1155/2015/460610. [87] R. a Sari, S. Taysi, O. Yilmaz, N. Bakan, Correlation of serum levels of adenosine deaminase activity and its isoenzymes with disease activity in rheumatoid arthritis., Clin. Exp. Rheumatol. 21 (2003) 87–90. [88] N. Živković, B. Djindjić, S. Stojanović, I. Krstić, I. Ćirić, T. Kostić, G. Kocić, 5′nucleotidase and adenosine deaminase in patients with rheumatoid arthritis, Vojnosanit. Pregl. 74 (2017). doi:10.2298/VSP151125267Z.

25

Journal Pre-proof [89] B. Erer, G. Yilmaz, F.M. Yilmaz, S. Koklu, Assessment of adenosine deaminase levels in rheumatoid arthritis patients receiving anti-TNF-α therapy, Rheumatol. Int. 29 (2009) 651–654. doi:10.1007/s00296-008-0750-1. [90] Z. Gao, G. Zhao, Z. Zhang, J. Huang, Z. Li, H. Zhang, K. Dong, Serum adenosine deaminase activity is increased in systemic lupus erythematosus patients and correlated

of

with disease activity, Immunol. Res. 66 (2018) 299–304. doi:10.1007/s12026-018-8984-9.

ro

[91] R. Saghiri, N. Ghashghai, S. Movaseghi, P. Poursharifi, S. Jalilfar, M.A. Bidhendi, L.

-p

Ghazizadeh, M. Ebrahimi-Rad, Serum adenosine deaminase activity in patients with systemic lupus erythematosus: A study based on ADA1 and ADA2 isoenzymes pattern,

re

Rheumatol. Int. 32 (2012) 1633–1638. doi:10.1007/s00296-011-1836-8.

lP

[92] K. Erkiliç, C. Evereklioglu, M. Çekmen, A. Özkiris, F. Duygulu, H. Dogan, Adenosine

na

deaminase enzyme activity is increased and negatively correlates with catalase, superoxide dismutase and glutathione peroxidase in patients with Behçet’s disease:

ur

Original contributions/clinical and laboratory investigations, Mediators Inflamm. 12

Jo

(2003) 107–116. doi:10.1080/0962935031000097754. [93] S. Söǧüt, E. Aydin, H. Elyas, N. Aksoy, H. Özyurt, Y. Totan, Ö. Akyol, The activities of serum adenosine deaminase and xanthine oxidase enzymes in Behcet’s disease, Clin. Chim. Acta. 325 (2002) 133–138. doi:10.1016/S0009-8981(02)00278-4. [94] B. Nikkhoo, N. Sigari, B. Ghaderi, A. Afkhamzadeh, N.A. Azadi, B. Mohsenpour, F. Fathi, M. Abdi, Diagnostic utility of adenosine deaminase in serum and bronchoalveolar lavage fluid for screening lung cancer in western Iran, J. Med. Biochem. 32 (2013) 109– 115. doi:10.2478/jomb-2013-0011. 26

Journal Pre-proof [95] D.C. Kelgandre, J. Pathak, S. Patel, P. Ingale, N. Swain, Adenosine deaminase - A novel diagnostic and prognostic biomarker for oral squamous cell carcinoma, Asian Pacific J. Cancer Prev. 17 (2016) 1865–1868. doi:10.7314/APJCP.2016.17.4.1865. [96] N. Pirinççi, T.Y. Kaya, M. Kaba, T. Ozan, İ. Geçit, H. Özveren, H. Eren, K. Ceylan, Serum adenosine deaminase, catalase, and carbonic anhydrase activities in patients with

of

renal cell carcinoma, Redox Rep. 22 (2017) 252–256.

ro

doi:10.1080/13510002.2016.1207364.

-p

[97] M. Ebrahimi-Rad, S. Khatami, S. Ansari, S. Jalylfar, S. Valadbeigi, R. Saghiri, Adenosine Deaminase 1 as a Biomarker for Diagnosis and Monitoring of Patients with Acute

re

Lymphoblastic Leukemia, J. Med. Biochem. 37 (2018) 128–133. doi:10.1515/jomb-2017-

lP

0042.

na

[98] M. Aghaei, F. Karami-Tehrani, S. Salami, M. Atri, Diagnostic Value of Adenosine Deaminase Activity in Benign and Malignant Breast Tumors, Arch. Med. Res. 41 (2010)

ur

14–18. doi:10.1016/j.arcmed.2009.10.012.

Jo

[99] S. Kaya, E.S. Cetin, B.C. Aridogan, S. Arikan, M. Demirci, Adenosine deaminase activity in serum of patients with hepatitis -- a useful tool in monitoring clinical status., J. Microbiol. Immunol. Infect. 40 (2007) 288–92. http://www.ncbi.nlm.nih.gov/pubmed/17712462. [100] M. Torgutalp, C. Efe, H. Babaoglu, T. Kav, Relationship between serum adenosine deaminase levels and liver histology in autoimmune hepatitis, World J. Gastroenterol. 23 (2017) 3876–3882. doi:10.3748/wjg.v23.i21.3876.

27

Journal Pre-proof [101] M. Gulec, H. Akin, H. Yuce H, E. Ergin, H. Elyas, O. Yalcin, O. Akyol, G. M., A. H., Y. H., E. E., E. H., Y. O., A. O., Adenosine deaminase and xanthine oxidase activities in bladder washing fluid from patients with bladder cancer: a preliminary study., Clin. Biochem. 36 (2003) 193–196. [102] I. Durak, H. Perk, M. Kavutçu, O. Canbolat, Ö. Akyol, Y. Bedük, Adenosine deaminase,

of

5′nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in

825–831. doi:10.1016/0891-5849(94)90199-6.

ro

cancerous and noncancerous human bladder tissues, Free Radic. Biol. Med. 16 (1994)

-p

[103] A. Eroğlu, O. Canbolat, S. Demirci, H. Kocaoglu, Y. Eryavuz, H. Akgul, Activities of

re

adenosine deaminase and 5’-nucleotidase in cancerous and noncancerous human

lP

colorectal tissues, Med. Oncol. 17 (2000) 319–324. doi:10.1007/BF02782198.

na

[104] M. Mahajan, N. Tiwari, R. Sharma, S. Kaur, N. Singh, Oxidative stress and its relationship with adenosine deaminase activity in various stages of breast cancer, Indian J.

ur

Clin. Biochem. (2013). doi:10.1007/s12291-012-0244-5.

Jo

[105] S. Chittiprol, P. Satishchandra, R.S. Bhimasenarao, G.R. Rangaswamy, S. V. Sureshbabu, D.K. Subbakrishna, K.S. Satish, A. Desai, V. Ravi, K.T. Shetty, Plasma adenosine deaminase activity among HIV1 Clade C seropositives: Relation to CD4 T cell population and antiretroviral therapy, Clin. Chim. Acta. 377 (2007) 133–137. doi:10.1016/j.cca.2006.09.006. [106] C. Gakis, G. Calia, A. Naitana, D. Pirino, G. Serru, Serum adenosine deaminase activity in HIV positive subjects. A hypothesis on the significance of ADA2., Panminerva Med. 31 (1989) 107–13. 28

Journal Pre-proof [107] M. Abdi, R. Rahbari, Z. Khatooni, N. Naseri, A. Najafi, I. Khodadadi, Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections, J. Clin. Lab. Anal. 30 (2016) 200–203. doi:10.1002/jcla.21836. [108] M.A. Iñigo, M. Ruiz López de Tejada, M. Torres-Tortosa, A. Sánchez-Porto, I. Ugarte, E.

of

García de Lomas, A. Morán Nestares, [Serum adenosine deaminase in human immunodeficiency virus infection. Its relationship with CD4+ lymphocytes and beta 2-

-p

ro

microglobulin]., Med. Clin. (Barc). 99 (1992) 766–8.

[109] J.G. Niedzwicki, N.M. Kouttab, K.H. Mayer, C.C. Carpenter, R.E. Parks, E. Abushanab,

re

D.R. Abernethy, Plasma adenosine deaminase2: a marker for human immunodeficiency

lP

virus infection., J. Acquir. Immune Defic. Syndr. 4 (1991) 178–82.

na

[110] U. Saracoglu, O. Guven, I. Durak, Adenosine deaminase and 5’-nucleotidase activities in saliva from patients with oral and laryngeal cancer, Oral Dis. 11 (2005) 323–325.

ur

doi:10.1111/j.1601-0825.2005.01131.x.

Jo

[111] S. Adanin, I. V Yalovetskiy, B.A. Nardulli, A.D. Sam 2nd, Z.S. Jonjev, W.R. Law, Inhibiting adenosine deaminase modulates the systemic inflammatory response syndrome in endotoxemia and sepsis, Am J Physiol Regul Integr Comp Physiol. 282 (2002) R132432. doi:10.1152/ajpregu.00373.2001. [112] G. Haskó, B. Cronstein, Regulation of Inflammation by Adenosine, Front. Immunol. 4 (2013) 85. doi:10.3389/fimmu.2013.00085. [113] L. Antonioli, R. Colucci, C. La Motta, M. Tuccori, O. Awwad, F. Da Settimo, C.

29

Journal Pre-proof Blandizzi, M. Fornai, Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders., Curr. Drug Targets. 13 (2012) 842–62. [114] M.L. Trincavelli, Unveiling the binding mode of adenosine deaminase inhibitors to the active site of the enzyme: Implication for rational drug design: Presented by Maria P.

of

Abbracchio, Purinergic Signal. 9 (2013) 1–3. doi:10.1007/s11302-013-9353-8.

ro

[115] E. Uzar, O. Sahin, H.R. Koyuncuoglu, E. Uz, O. Bas, S. Kilbas, H.R. Yilmaz, V.A.

-p

Yurekli, H. Kucuker, A. Songur, The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: Protective effect of caffeic

re

acid phenethyl ester, Toxicology. 218 (2006) 125–133. doi:10.1016/j.tox.2005.10.014.

lP

[116] R. Glazer, Adenosine deaminase inhibitors: Their role in chemotherapy and

na

immunosuppression, Cancer Chemother. Pharmacol. 4 (1980) 227–235.

ur

doi:10.1007/BF00255266.

[117] G. Li, I. Nakagome, S. Hirono, T. Itoh, R. Fujiwara, Inhibition of adenosine deaminase

Jo

(ADA)-mediated metabolism of cordycepin by natural substances, Pharmacol. Res. Perspect. 3 (2015) 1–11. doi:10.1002/prp2.121. [118] V. Tardif, R. Muir, R. Cubas, M. Chakhtoura, P. Wilkinson, T. Metcalf, R. Herro, E.K. Haddad, Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV, Nat. Commun. (2019). doi:10.1038/s41467-019-08801-1. [119] G. Cristalli, S. Costanzi, C. Lambertucci, G. Lupidi, S. Vittori, R. Volpini, E. Camaioni, Adenosine deaminase: functional implications and different classes of inhibitors., Med.

30

Journal Pre-proof Res. Rev. 21 (2001) 105–28. [120] Y. Honma, A Novel Therapeutic Strategy Against Monocytic Leukemia with Deoxyadenosine Analogs and Adenosine Deaminase Inhibitors, Leuk. Lymphoma. 42 (2001) 953–962. doi:10.3109/10428190109097714. [121] J.B. Johnston, Mechanism of Action of Pentostatin and Cladribine in Hairy Cell

of

Leukemia, Leuk. Lymphoma. 52 (2011) 43–45. doi:10.3109/10428194.2011.570394.

ro

[122] J.E. Dimsdale, D. Norman, D. DeJardin, M.S. Wallace, The effect of opioids on sleep

-p

architecture., J. Clin. Sleep Med. 3 (2007) 33–6.

re

[123] J.A. Robertson, R.J. Purple, P. Cole, Z. Zaiwalla, K. Wulff, K.T.S. Pattinson, Sleep

lP

disturbance in patients taking opioid medication for chronic back pain, Anaesthesia. 71

na

(2016) 1296–1307. doi:10.1111/anae.13601. [124] J.T. Moore, M.B. Kelz, Opiates, sleep, and pain: the adenosinergic link., Anesthesiology.

ur

111 (2009) 1175–6. doi:10.1097/ALN.0b013e3181bdfa2e.

Jo

[125] R.E. Brown, R. Basheer, J.T. McKenna, R.E. Strecker, R.W. McCarley, Control of Sleep and Wakefulness, Physiol. Rev. 92 (2012) 1087–1187. doi:10.1152/physrev.00032.2011. [126] A.M. Nelson, A.S. Battersby, H.A. Baghdoyan, R. Lydic, Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase, Anesthesiology. 111 (2009) 1327–1333. doi:10.1097/ALN.0b013e3181bdf894. [127] T. Roehrs, T. Roth, Sleep and Pain: Interaction of Two Vital Functions, Semin. Neurol. 25 (2005) 106–116. doi:10.1055/s-2005-867079.

31

Journal Pre-proof [128] B. Kundermann, J.-C. Krieg, W. Schreiber, S. Lautenbacher, The effect of sleep deprivation on pain., Pain Res. Manag. 9 (2004) 25–32. [129] R.M. Gallagher, L.J. Rosenthal, Chronic Pain and Opiates: Balancing Pain Control and Risks in Long-Term Opioid Treatment, Arch. Phys. Med. Rehabil. 89 (2008) S77–S82. doi:10.1016/j.apmr.2007.12.003.

of

[130] M. Garcia-Gil, M.G. Tozzi, S. Varani, L. Della Verde, E. Petrotto, F. Balestri, L.

ro

Colombaioni, M. Camici, The combination of adenosine deaminase inhibition and

-p

deoxyadenosine induces apoptosis in a human astrocytoma cell line, Neurochem. Int. 80

re

(2015) 14–22. doi:10.1016/j.neuint.2014.11.005.

[131] M. Garcia-Gil, M.G. Tozzi, S. Allegrini, S. Folcarelli, G. Della Sala, V. Voccoli, L.

lP

Colombaioni, M. Camici, Novel metabolic aspects related to adenosine deaminase

na

inhibition in a human astrocytoma cell line, Neurochem. Int. 60 (2012) 523–532.

ur

doi:10.1016/j.neuint.2012.02.008.

[132] M. Garcia-Gil, M.G. Tozzi, F. Balestri, L. Colombaioni, M. Camici, Mitochondrial

Jo

Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines, J. Cell. Biochem. 117 (2016) 1671–1679. doi:10.1002/jcb.25460. [133] M. Garcia-Gil, M. Camici, S. Allegrini, R. Pesi, E. Petrotto, M. Tozzi, M. Garcia-Gil, M. Camici, S. Allegrini, R. Pesi, E. Petrotto, M.G. Tozzi, Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors, Int. J. Mol. Sci. 19 (2018) 3598. doi:10.3390/ijms19113598.

32

Journal Pre-proof [134] B. Kutryb-Zajac, P. Koszalka, P. Mierzejewska, A. Bulinska, M.A. Zabielska, K. Brodzik, A. Skrzypkowska, L. Zelazek, I. Pelikant-Malecka, E.M. Slominska, R.T. Smolenski, Adenosine deaminase inhibition suppresses progression of 4T1 murine breast cancer by adenosine receptor-dependent mechanisms, J. Cell. Mol. Med. 22 (2018) 5939–5954. doi:10.1111/jcmm.13864.

of

[135] L. Antonioli, M. Fornai, R. Colucci, N. Ghisu, F. Da Settimo, G. Natale, O. Kastsiuchenka, E. Duranti, A. Virdis, C. Vassalle, C. La Motta, L. Mugnaini, M.C.

ro

Breschi, C. Blandizzi, M. Del Taca, Inhibition of Adenosine Deaminase Attenuates

-p

Inflammation in Experimental Colitis, J. Pharmacol. Exp. Ther. 322 (2007) 435–442.

re

doi:10.1124/jpet.107.122762.

lP

[136] L. Antonioli, M. Fornai, R. Colucci, O. Awwad, N. Ghisu, M. Tuccori, F. Da Settimo, C. La Motta, G. Natale, E. Duranti, A. Virdis, C. Blandizzi, The Blockade of Adenosine

na

Deaminase Ameliorates Chronic Experimental Colitis through the Recruitment of

ur

Adenosine A2A and A3 Receptors, J. Pharmacol. Exp. Ther. 335 (2010) 434–442.

Jo

doi:10.1124/jpet.110.171223.

[137] A.F.T. De Araújo Junqueira, A.A. Martins Dias, M. Lima Vale, G.M.G. Turco Spilborghs, A. Siqueira Bossa, B. Bezerra Lima, A. Fiorini Carvalho, R. Littleton Guerrant, R. Albuquerque Ribeiro, G. Anne Brito, Adenosine deaminase inhibition prevents Clostridium difficile toxin A-induced enteritis in mice, Infect. Immun. 79 (2011) 653–662. doi:10.1128/IAI.01159-10. [138] R.T. DeGraw, B.D. Anderson, Enhanced oral bioavailability of 2′-β-fluoro2′,3′dideoxyadenosine (F-ddA) through local inhibition of intestinal adenosine deaminase,

33

Journal Pre-proof Pharm. Res. 18 (2001) 1270–1276. doi:10.1023/A:1013029726065. [139] D. Singhal, B.D. Anderson, Optimization of the local inhibition of intestinal adenosine deaminase (ADA) by erythro-9-(2-hydroxy-3-nonyl)adenine: Enhanced oral delivery of an ADA-activated prodrug for anti-HIV therapy, J. Pharm. Sci. 87 (1998) 578–585. doi:10.1021/js970377b.

of

[140] K. Köse, S. Utaş, C. Yazici, A. Akdaş, F. Keleştimur, Effect of propylthiouracil on

ro

adenosine deaminase activity and thyroid function in patients with psoriasis., Br. J.

-p

Dermatol. 144 (2001) 1121–6.

re

[141] F.E. Yıldırım, A. Karaduman, A. Pinar, Y. Aksoy, CD26/dipeptidyl-peptidase IV and adenosine deaminase serum levels in psoriatic patients treated with cyclosporine,

lP

etanercept, and psoralen plus ultraviolet A phototherapy, Int. J. Dermatol. 50 (2011) 948–

na

955. doi:10.1111/j.1365-4632.2010.04799.x.

ur

[142] E.S. Cohen, W.R. Law, C.R. Easington, K.Q. Cruz, B.A. Nardulli, R.A. Balk, J.E. Parrillo, S.M. Hollenberg, Adenosine deaminase inhibition attenuates microvascular

Jo

dysfunction and improves survival in sepsis, Am. J. Respir. Crit. Care Med. 166 (2002) 16–20. doi:10.1164/rccm.200109-014OC. [143] N. Kayhan, B. Funke, L. Conzelmann, H. Winkler, S. Hofer, J. Steppan, H. Schmidt, H. Bardenheuer, C.-F. Vahl, M.A. Weigand, The adenosine deaminase inhibitor erythro-9-[2hydroxyl-3-nonyl]-adenine decreases intestinal permeability and protects against experimental sepsis: a prospective, randomised laboratory investigation, Crit. Care. 12 (2008) R125. doi:10.1186/cc7033.

34

Journal Pre-proof [144] W.R. Law, B.A. Conlon, J.D. Ross, The extracellular cardiac purine metabolome in sepsis., Shock. 28 (2007) 259–264. doi:10.1097/01.shk.0000232587.61871.1b. [145] W.R. Law, V.E. Valli, B.A. Conlon, Therapeutic potential for transient inhibition of adenosine deaminase in systemic inflammatory response syndrome, Crit Care Med. 31 (2003) 1475–1481. doi:10.1097/01.CCM.0000063259.09580.D8.

of

[146] Y. Nakajima, T. Kanno, T. Nagaya, K. Kuribayashi, T. Nakano, A. Gotoh, T. Nishizaki,

ro

Adenosine Deaminase Inhibitor EHNA Exhibits a Potent Anticancer Effect Against

-p

Malignant Pleural Mesothelioma, Cell. Physiol. Biochem. 35 (2015) 51–60.

re

doi:10.1159/000369674.

[147] D. Mistry, M.G. Chambers, R.M. Mason, The role of adenosine in chondrocyte death in

lP

murine osteoarthritis and in a murine chondrocyte cell line, Osteoarthr. Cartil. 14 (2006)

na

486–495. doi:10.1016/j.joca.2005.11.015.

ur

[148] E.H. Kraut, J.C. Neff, B.A. Bouroncle, D. Gochnour, M.R. Grever, Immunosuppressive

Jo

effects of pentostatin, J. Clin. Oncol. 8 (1990) 848–855. doi:10.1200/JCO.1990.8.5.848. [149] E. Giovannucci, a Ascherio, E.B. Rimm, M.J. Stampfer, G. a Colditz, W.C. Willett, Intake of carotenoids and retinol in relation to risk of prostate cancer., J. Natl. Cancer Inst. 87 (1995) 1767–1776. doi:10.1093/jnci/87.23.1767. [150] R.B. Van Breemen, X. Xu, M.A. Viana, L. Chen, M. Stacewicz-Sapuntzakis, C. Duncan, P.E. Bowen, R. Sharifi, Liquid chromatography - Mass spectrometry of cis- and all-translycopene in human serum and prostate tissue after dietary supplementation with tomato sauce, J. Agric. Food Chem. 50 (2002) 2214–2219. doi:10.1021/jf0110351.

35

Journal Pre-proof [151] E. Giovannucci, E.B. Rimm, Y. Liu, M.J. Stampfer, W.C. Willett, A Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk, J. Natl. Cancer Inst. 94 (2002) 391–398. doi:10.1093/jnci/94.5.391. [152] Q.Y. Lu, J.C. Hung, D. Heber, V.L.W. Go, V.E. Reuter, C. Cordon-Cardo, H.I. Scher, J.R. Marshall, Z.F. Zhang, Inverse associations between plasma lycopene and other

of

carotenoids and prostate cancer, Cancer Epidemiol. Biomarkers Prev. 10 (2001) 749–756.

ro

[153] P.H. Gann, J. Ma, E. Giovannucci, W. Willett, F.M. Sacks, C.H. Hennekens, M.J.

-p

Stampfer, Lower prostate cancer risk in men with elevated plasma lycopene levels: results

re

of a prospective analysis., Cancer Res. 59 (1999) 1225–30. [154] K. Zu, L. Mucci, B.A. Rosner, S.K. Clinton, M. Loda, M.J. Stampfer, E. Giovannucci,

lP

Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the

na

Prostate-Specific Antigen Era, JNCI J. Natl. Cancer Inst. 106 (2014) djt430–djt430.

ur

doi:10.1093/jnci/djt430.

[155] N. Holzapfel, B. Holzapfel, S. Champ, J. Feldthusen, J. Clements, D. Hutmacher, The

Jo

Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence, Int. J. Mol. Sci. 14 (2013) 14620–14646. doi:10.3390/ijms140714620. [156] Chen, Y. Song, L. Zhang, Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies., J Nutr Sci Vitaminol. 59 (2013) 213–23. [157] I. Durak, H. Biri, A. Avci, S. Sözen, E. Devrim, Tomato juice inhibits adenosine

36

Journal Pre-proof deaminase activity in human prostate tissue from patient with prostate cancer, Nutr. Res. 23 (2003) 1183–1188. doi:10.1016/S0271-5317(03)00115-5. [158] L. Konrad, H.-H. Müller, C. Lenz, H. Laubinger, G. Aumüller, J.J. Lichius, Antiproliferative Effect on Human Prostate Cancer Cells by a Stinging Nettle Root (Urtica dioica) Extract, Planta Med. 66 (2000) 44–47. doi:10.1055/s-2000-11117.

of

[159] I. Durak, H. Biri, E. Devrim, S. Sözen, A. Avci, Aqueous extract of Urtica Dioica makes

ro

significant inhibition on adenosine deaminase activity in prostate tissue from patients with

-p

prostate cancer, Cancer Biol. Ther. 3 (2004) 855–857. doi:10.4161/cbt.3.9.1038.

re

[160] K.S. De Bona, L.P. Bellé, M.H. Sari, G. Thomé, M.R.C. Schetinger, V.M. Morsch, A. Boligon, M.L. Athayde, A.S. Pigatto, M.B. Moretto, Syzygium Cumini Extract Decrease

lP

Adenosine Deaminase, 5′Nucleotidase Activities and Oxidative Damage in Platelets of

na

Diabetic Patients, Cell. Physiol. Biochem. 26 (2010) 729–738. doi:10.1159/000322340.

ur

[161] K. Sharafeldin, M.R. Rizvi, Effect of traditional plant medicines (Cinnamomum zeylanicum and Syzygium cumini) on oxidative stress and insulin resistance in

Jo

streptozotocin-induced diabetic rats, J. Basic Appl. Zool. 72 (2015) 126–134. doi:10.1016/j.jobaz.2015.09.002. [162] A. Bopp, K.S. De Bona, L.P. Bell??, R.N. Moresco, M.B. Moretto, Syzygium cumini inhibits adenosine deaminase activity and reduces glucose levels in hyperglycemic patients, Fundam. Clin. Pharmacol. 23 (2009) 501–507. doi:10.1111/j.14728206.2009.00700.x. [163] P.E.R. Bitencourt, K.S. De Bona, L.O. Cargnelutti, G. Bonfanti, A. Pigatto, A. Boligon,

37

Journal Pre-proof M.L. Athayde, F. Pierezan, R.A. Zanette, M.B. Moretto, Syzygium cumini seed extract ameliorates adenosine deaminase activity and biochemical parameters but does not alter insulin sensitivity and pancreas architecture in a short-term model of diabetes, J. Complement. Integr. Med. 12 (2015) 187–93. doi:10.1515/jcim-2015-0008. [164] L.O. Cargnelutt, P.E.R. Bitencourt, G. Bochi, T. Duarte, A. Boligon, A.S. Pigatto, M.L.

of

Athayde, R.N. Moresco, M.B. Moretto, Syzygium cumini Leaf Extract Protects Against Ethanol-Induced Acute Injury in Rats by Inhibiting Adenosine Deaminase Activity and

ro

Proinflammatory Cytokine Production, Res. J. Phytochem. 9 (2015) 56–67.

-p

doi:10.3923/rjphyto.2015.56.67.

re

[165] L.P. Bellé, P.E.R. Bitencourt, F.H. Abdalla, K. Santos de Bona, A. Peres, L.D.K. Maders,

lP

M.B. Moretto, Aqueous seed extract of Syzygium cumini inhibits the dipeptidyl peptidase IV and adenosine deaminase activities, but it does not change the CD26 expression in

ur

0195-6.

na

lymphocytes in vitro, J. Physiol. Biochem. 69 (2013) 119–124. doi:10.1007/s13105-012-

Jo

[166] A.K. Sharma, A. Munajjam, B. Vaishnav, R. Sharma, A. Sharma, K. Kishore, A. Sharma, D. Sharma, R. Kumari, A. Tiwari, S.K. Singh, S. Gaur, V.S. Jatav, B.P. Srinivasan, S.S. Agarwal, Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury, J. Biomed. Res. 26 (2012) 24–36. doi:10.1016/S1674-8301(12)60004-9. [167] H.P. Koch, W. Jäger, U. Groh, G. Plank, In vitro inhibition of adenosine deaminase by flavonoids and related compounds. New insight into the mechanism of action of plant

38

Journal Pre-proof phenolics., Methods Find. Exp. Clin. Pharmacol. 14 (1992) 413–7. [168] H.P. Koch, W. Jäger, J. Hysek, B. Körpert, Garlic and onion extracts. In vitro inhibition of adenosine deaminase, Phyther. Res. 6 (1992) 50–52. doi:10.1002/ptr.2650060113. [169] H.P. Koch, W. Jäger, U. Groh, J.E. Hovie, G. Plank, U. Sedlak, W. Praznik, Carbohydrates from garlic bulbs (Allium sativum L.) as inhibitors of adenosine deaminase

of

enzyme activity, Phyther. Res. 7 (1993) 387–389. doi:10.1002/ptr.2650070514.

ro

[170] M.F. Melzig, E. Krause, S. Franke, Inhibition of adenosine deaminase activity of aortic

-p

endothelial cells by extracts of garlic (Allium sativum L.)., Pharmazie. 50 (1995) 359–61.

re

[171] R. Kumar, S. Chhatwal, S. Arora, S. Sharma, J. Singh, N. Singh, V. Bhandari, A.

lP

Khurana, Antihyperglycemic, antihyperlipidemic, anti-inflammatory and adenosine deaminase-lowering effects of garlic in patients with type 2 diabetes mellitus with obesity,

na

Diabetes, Metab. Syndr. Obes. Targets Ther. 6 (2013) 49–56.

ur

[172] H.H. Herfarth, M.D. Kappelman, M.D. Long, K.L. Isaacs, Use of Methotrexate in the

Jo

Treatment of Inflammatory Bowel Diseases, Inflamm. Bowel Dis. 22 (2016) 224–233. doi:10.1097/MIB.0000000000000589. [173] B.N. Cronstein, The antirheumatic agents sulphasalazine and methotrexate share an antiinflammatory mechanism, Rheumatol. (United Kingdom). 34 (1995) 30–32. doi:10.1093/rheumatology/XXXIV.suppl_4.30. [174] C.T. Quinn, J.C. Griener, T. Bottiglieri, E. Arning, N.J. Winick, Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid, J. Pediatr. Hematol. Oncol. 26 (2004) 386–388. doi:10.1097/00043426-200406000-00011. 39

Journal Pre-proof [175] S. Vezmar, A. Becker, U. Bode, U. Jaehde, Biochemical and Clinical Aspects of Methotrexate Neurotoxicity, Chemotherapy. 49 (2003) 92–104. doi:10.1159/000069773. [176] F. V. Pinheiro, V.C. Pimentel, K.S. De Bona, G. Scola, M. Salvador, C. Funchal, M.B. Moretto, Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: Protective effects of grape seed extract,

of

Cell Biochem. Funct. 28 (2010) 89–94. doi:10.1002/cbf.1627.

ro

[177] Y. Shimada, K. Sato, T. Takeda, Y. Tokuji, The Organogermanium Compound Ge-132

-p

Interacts with Nucleic Acid Components and Inhibits the Catalysis of Adenosine Substrate

doi:10.1007/s12011-017-1020-4.

re

by Adenosine Deaminase, Biol. Trace Elem. Res. 181 (2018) 164–172.

lP

[178] B.J. Kaplan, W.W. Parish, G.M. Andrus, J.S.A. Simpson, C.J. Field, Germane Facts

na

About Germanium Sesquioxide: I. Chemistry and Anticancer Properties, J. Altern.

ur

Complement. Med. 10 (2004) 337–344. doi:10.1089/107555304323062329. [179] F. Suzuki, R.R. Brutkiewicz, R.B. Pollard, Ability of sera from mice treated with Ge-132,

Jo

an organic germanium compound, to inhibit experimental murine ascites tumours., Br. J. Cancer. 52 (1985) 757–63. [180] T. Nakamura, T. Takeda, Y. Tokuji, The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice, Int. J. Vitam. Nutr. Res. 84 (2014) 183– 95. doi:10.1024/0300-9831/a000205. [181] T. Nakamura, M. Saito, H. Aso, Effects of a Lactobacilli, Oligosaccharide and Organic

40

Journal Pre-proof Germanium Intake on the Immune Responses of Mice, Biosci Biotechnol Biochem. 76 (2012) 375–7. doi:10.1271/bbb.110655. [182] S.K. Mishra, J.P. Sah, G. Awasthi, R. Sharma, Adenosine deaminase activity in Plasma of Children with Acute Lymphoblastic Leukemia, J. Nepal Health Res. Counc. 7 (2010) 93– 7. doi:10.33314/jnhrc.200.

of

[183] Z. a Oztürk, S. Köklü, M.F. Erol, F.M. Yilmaz, O. Basar, O. Yüksel, G. Yilmaz, B.

ro

Kisacik, I. Yüksel, Serum adenosine deaminase levels in diagnosis of acute appendicitis.,

-p

Emerg. Med. J. 25 (2008) 583–5. doi:10.1136/emj.2007.054452.

re

[184] J.S. Muhammad, M. Ishaq, M. Ishaq, K. Ahmed, Genetics and Epigenetics Mechanism in the Pathogenesis of Behçet’s Disease, Curr. Rheumatol. Rev. 15 (2019) 7–13.

lP

doi:10.2174/1573397114666180521090335.

na

[185] N. Pirinççi, I. Geçit, M. Güneş, M.B. Yüksel, M. Kaba, S. Tanık, H. Demir, M. Aslan,

ur

Serum adenosine deaminase, catalase and carbonic anhydrase activities in patients with bladder cancer., Clinics (Sao Paulo). 67 (2012) 1443–6.

Jo

doi:10.6061/CLINICS/2012(12)15. [186] M. Güleç, H. Akin, H. Yüce H, E. Ergin, H. Elyas, O. Yalçin, O. Akyol, Adenosine deaminase and xanthine oxidase activities in bladder washing fluid from patients with bladder cancer: a preliminary study., Clin. Biochem. 36 (2003) 193–6. [187] M. Walia, M. Mahajan, K. Singh, Serum adenosine deaminase, 5’-nucleotidase & alkaline phosphatase in breast cancer patients., Indian J. Med. Res. 101 (1995) 247–9. [188] A. Faisal, M. Taha, Serum adenosine deaminase activity in Iraqi patients with breast 41

Journal Pre-proof cancer on tamoxifen therapy, Gaziantep Med. J. 18 (2012) 139–142. doi:10.5455/GMJ30-2012-96. [189] O. Canbolat, I. Durak, R. Çetin, M. Kavutcu, S. Demirci, S. Öztürk, Activities of adenosine deaminase, 5′-nucleotidase, guanase, and cytidine deaminase enzymes in cancerous and non-cancerous human breast tissues, Breast Cancer Res. Treat. 37 (1996)

of

189–193. doi:10.1007/BF01806500.

ro

[190] U.P. Santosh, G.S. Renukananda, S. Abhilash, Role of Adenosine Deaminase in Common

-p

Chronic ENT Infections., J. Clin. Diagn. Res. 10 (2016) MC01-2.

re

doi:10.7860/JCDR/2016/18452.7347.

[191] P. Poursharifi, R. Saghiri, M. Ebrahimi-Rad, H. Nazem, Z. Pourpak, M. Moin, S. Shams,

lP

Adenosine deaminase in patients with primary immunodeficiency syndromes: The

na

analysis of serum ADA1 and ADA2 activities, Clin. Biochem. 42 (2009) 1438–1443.

ur

doi:10.1016/j.clinbiochem.2008.10.019. [192] D. Vannoni, A. Bernini, F. Carlucci, S. Civitelli, M.C. Di Pietro, R. Leoncini, F. Rosi, A.

Jo

Tabucchi, G. Tanzini, E. Marinello, Enzyme activities controlling adenosine levels in normal and neoplastic tissues, Med. Oncol. 21 (2004) 187–195. doi:10.1385/MO:21:2:187. [193] V.K. Celik, I. Sari, A. Engin, Y. Gürsel, H. Aydin, S. Bakir, Determination of serum adenosine deaminase and xanthine oxidase levels in patients with crimean-congo hemorrhagic fever., Clinics (Sao Paulo). 65 (2010) 697–702. doi:10.1590/S180759322010000700008.

42

Journal Pre-proof [194] T. Hoshino, K. Yamada, K. Masuoka, I. Tsuboi, K. Itoh, K. Nonaka, K. Oizumi, Elevated adenosine deaminase activity in the serum of patients with diabetes mellitus., Diabetes Res. Clin. Pract. 25 (1994) 97–102. [195] N. Kurtul, S. Pence, E. Akarsu, H. Kocoglu, Y. Aksoy, H. Aksoy, Adenosine deaminase activity in the serum of type 2 diabetic patients., Acta Medica (Hradec Kralove). 47

of

(2004) 33–5.

ro

[196] L.B. Sapkota, S. Thapa, N. Subedi, Correlation study of adenosine deaminase and its

-p

isoenzymes in type 2 diabetes mellitus, BMJ Open Diabetes Res. Care. 5 (2017) e000357.

re

doi:10.1136/bmjdrc-2016-000357.

[197] B. Larijani, R. Heshmat, M. Ebrahimi-Rad, S. Khatami, S. Valadbeigi, R. Saghiri,

lP

Diagnostic Value of Adenosine Deaminase and Its Isoforms in Type II Diabetes Mellitus,

na

Enzyme Res. 2016 (2016) 1–6. doi:10.1155/2016/9526593.

ur

[198] V.K. Khemka, D. Bagchi, A. Ghosh, O. Sen, A. Bir, S. Chakrabarti, A. Banerjee, Raised serum adenosine deaminase level in nonobese type 2 diabetes mellitus, Sci. World J. 2013

Jo

(2013) 1–5. doi:10.1155/2013/404320. [199] N.M. Elsherbiny, M. Naime, S. Ahmad, A.M. Elsherbini, S. Mohammad, S. Fulzele, A.B. El-Remessy, M.M. Al-Gayyar, L.A. Eissa, M.M. El-Shishtawy, G. Han, R. White, T.F. Haroldo, G.I. Liou, Potential roles of adenosine deaminase-2 in diabetic retinopathy, Biochem. Biophys. Res. Commun. 436 (2013) 355–361. doi:10.1016/j.bbrc.2013.05.023. [200] M. Shiva Prakash, S. Chennaiah, Y. Murthy, E. Anjaiah, S. Ananda Rao, C. Suresh, Altered adenosine deaminase activity in type 2 diabetes mellitus, Journal, Indian Acad.

43

Journal Pre-proof Clin. Med. 7 (2006) 114–117. [201] Y.A. Samra, H.M. Saleh, K.A. Hussein, N.M. Elsherbiny, A.S. Ibrahim, K. Elmasry, S. Fulzele, M.M. El-Shishtawy, L.A. Eissa, M. Al-Shabrawey, G.I. Liou, Adenosine deaminase-2–induced hyperpermeability in human retinal vascular endothelial cells is suppressed by microRNA-146b-3p, Investig. Ophthalmol. Vis. Sci. 58 (2017) 933–943.

of

doi:10.1167/iovs.16-19782.

ro

[202] S. Fulzele, A. El-Sherbini, S. Ahmad, R. Sangani, S. Matragoon, A. El-Remessy, R.

-p

Radhakrishnan, G.I. Liou, MicroRNA-146b-3p Regulates Retinal Inflammation by Suppressing Adenosine Deaminase-2 in Diabetes, Biomed Res. Int. 2015 (2015) 1–8.

re

doi:10.1155/2015/846501.

lP

[203] I. Durak, R. Cetin, O. Canbolat, D. Cetin, Z. Yurtarslani, A. Ünal, Adenosine deaminase,

na

5′-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients

ur

with gastric cancer, Cancer Lett. 84 (1994) 199–202. doi:10.1016/0304-3835(94)90376-X. [204] G. Ri, S. Ohno, M. Furutani, Y. Furutani, T. Tsukahara, N. Hagita, H. Haruyama, S.

Jo

Nakamura, T. Yamamoto, R. Matsuoka, An indication for correlation between the serum ADA level and gastric cancer risk., Anticancer Res. 30 (2010) 2347–9. [205] Y. Beyazit, S. Koklu, A. Tas, T. Purnak, A. Sayilir, M. Kurt, T. Turhan, T. Celik, B. Suvak, S. Torun, E. Akbal, Serum adenosine deaminase activity as a predictor of disease severity in ulcerative colitis, J. Crohn’s Colitis. 6 (2012) 102–107. doi:10.1016/j.crohns.2011.07.010. [206] B. Cakal, Y. Beyazit, S. Koklu, E. Akbal, I. Biyikoglu, G. Yilmaz, Elevated adenosine

44

Journal Pre-proof deaminase levels in celiac disease, J. Clin. Lab. Anal. 24 (2010) 323–326. doi:10.1002/jcla.20410. [207] R. Mishra, M.K. Agarwal, J.P. Chansuria, Serum adenosine deaminase levels as an index of tumor growth in head and neck malignancy, Indian J Otolaryngol Head Neck Surg. 52 (2000) 360–363. doi:10.1007/BF02991478.

of

[208] E. Azimi, F. Zarei, S. ValadBeigi, S.M. Athari, M. Bakhtairy, R. Shaghiri, Adenosine

ro

deaminase (ADA) activity and isozymes in the serum of patients with hepatitis B

-p

compared with healthy people: a useful method in diagnosis clinical status, Arch. Med.

re

Lab. Sci. 3 (2017) 15–20. doi:10.22037/amls.v3i1.17482. [209] T. Kiran, A. Karabulut, I. Sahin, C. Colak, Evaluation of Oxidative Stress Status and

lP

Adenosine Deaminase Activity in Hyperthyroid and Hypothyroid Patients, Med. Sci. | Int.

na

Med. J. 3 (2014) 1595. doi:10.5455/medscience.2014.03.8155.

ur

[210] S. Sharma, P.B. Desai, R.B. Metgudmath, Evaluation of Serum Adenosine Deaminase and

Jo

Retinol in patients with Laryngeal Cancer, Indian J.Pharm.Biol.Res. 1 (2013) 30–34. [211] Y. Ogat, K. Aoe, A. Hiraki, K. Murakami, D. Kishino, K. Chikamori, T. Maeda, H. Ueoka, K. Kiura, M. Tanimoto, Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis?, Acta Med. Okayama. 65 (2011) 259–263. doi:10.18926/AMO/46851. [212] N.A. Helmy, S.A. Eissa, H.H. Masoud, A.F. Elessawy, R.I. Ahmed, Diagnostic value of adenosine deaminase in tuberculous and malignant pleural effusion, Egypt. J. Chest Dis.

45

Journal Pre-proof Tuberc. 61 (2012) 413–417. doi:10.1016/j.ejcdt.2012.08.004. [213] K. Dimakou, G. Hillas, P. Bakakos, Adenosine deaminase activity and its isoenzymes in the sputum of patients with pulmonary tuberculosis., Int. J. Tuberc. Lung Dis. 13 (2009) 744–748. [214] F. Rostampour, M. Biglari, A. Vaisi-Raygani, S. Salimi, H. Tavilani, Adenosine

of

deaminase activity in fertile and infertile men, Andrologia. 44 (2012) 586–589.

ro

doi:10.1111/j.1439-0272.2011.01231.x.

-p

[215] A.J. Akinyemi, P.K. Okonkwo, O.A. Faboya, S.A. Onikanni, A. Fadaka, I. Olayide, E.O.

re

Akinyemi, G. Oboh, Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities

lP

in a rat model, Metab. Brain Dis. 32 (2017) 87–95. doi:10.1007/s11011-016-9887-x.

na

[216] C.R.N. Polachini, R.M. Spanevello, E.A. Casali, D. Zanini, L.B. Pereira, C.C. Martins, J.

ur

Baldissareli, A.M. Cardoso, M.F. Duarte, P. da Costa, A.L.C. Prado, M.R.C. Schetinger, V.M. Morsch, Alterations in the cholinesterase and adenosine deaminase activities and

Jo

inflammation biomarker levels in patients with multiple sclerosis, Neuroscience. 266 (2014) 266–274. doi:10.1016/j.neuroscience.2014.01.048. [217] E.O. Chielle, G. Bonfanti, K.S. De Bona, R.N. Moresco, M.B. Moretto, Adenosine deaminase, dipeptidyl peptidase-IV activities and lipid peroxidation are increased in the saliva of obese young adult, Clin. Chem. Lab. Med. 53 (2015) 1041–1047. doi:10.1515/cclm-2014-1086. [218] K.S. Yerrajwala, V. Saradhini, B.R. Reddy, S. Gudimella, A study of Adenosine

46

Journal Pre-proof Deaminase and Gamma Glutamyl Transpeptidase in Acute Pancreatitis, Int. Arch. Integr. Med. 3 (2016) 162–167. [219] H. Herken, O. Akyol, H.R. Yilmaz, H. Tutkun, H.A. Savas, M.E. Ozen, A. Kalenderoglu, M. Gulec, Nitric oxide, adenosine deaminase, xanthine oxidase and superoxide dismutase in patients with panic disorder: Alterations by antidepressant treatment, Hum.

of

Psychopharmacol. 21 (2006) 53–59. doi:10.1002/hup.742.

ro

[220] S. Chiba, H. Matsumoto, M. Saitoh, M. Kasahara, M. Matsuya, M. Kashiwagi, A correlation study between serum adenosine deaminase activities and peripheral

-p

lymphocyte subsets in Parkinson’s disease, J. Neurol. Sci. 132 (1995) 170–173.

re

doi:10.1016/0022-510X(95)00136-P.

lP

[221] R. Yaǧci, A. Gürel, B.I. Ersöz, R. Karadaǧ, I.F. Hepşen, S. Duman, The activities of

na

paraoxonase, xanthine oxidase, adenosine deaminase and the level of nitrite in pseudoexfoliation syndrome, Ophthalmic Res. 42 (2009) 155–159.

ur

doi:10.1159/000229306.

Jo

[222] M. Hashemi, H. Mehrabifar, M. Daliri, S. Ghavami, Adenosine deaminase activity, trypsin inhibitory capacity and total antioxidant capacity in psoriasis, J. Eur. Acad. Dermatology Venereol. 24 (2010) 329–334. doi:10.1111/j.1468-3083.2009.03416.x. [223] Z. Erbagci, A.B. Erbagci, O. Köylüoglu, A.A. Tuncel, Serum Adenosine Deaminase Activity in Monitoring Disease Activity and Response to Therapy in Severe Psoriasis, Acta Medica (Hradec Kral. Czech Republic). (2006). doi:10.14712/18059694.2017.119. [224] Y.M. Moustafa, M.A. Elsaied, E.M. Abd-Elaaty, R.A. Elsayed, Evaluation of Serum

47

Journal Pre-proof Adenosine Deaminase and Inflammatory Markers in Psoriatic Patients., Indian J. Dermatol. 64 (2019) 207–212. doi:10.4103/ijd.IJD_420_17. [225] I. Ocaña, E. Ribera, J.M. Martinez-Vázquez, I. Ruiz, E. Bejarano, C. Pigrau, A. Pahissa, Adenosine deaminase activity in rheumatoid pleural effusion., Ann. Rheum. Dis. 47 (1988) 394–7.

ro

effusions, Acta Med. Scand. 215 (1984) 299–304.

of

[226] T. Pettersson, K. Ojala, T.. Weber, Adenosine deaminase in the diagnosis of pleural

-p

[227] E. Uechi, C. Nakata, T. Murayama, Y. Shiohira, AB0563 Analysis of Pleural Effusion

re

Adenosine Deaminase (ADA) Activity in Rheumatic Disease Patients, Ann. Rheum. Dis.

lP

74 (2015) 1088.2-1088. doi:10.1136/annrheumdis-2015-eular.2013. [228] Z. Zakeri, S. Izadi, A. Niazi, Z. Bari, S. Zendeboodi, M. Shakiba, M. Mashhadi, B.

na

Narouie, M. Ghasemi-Rad, Comparison of adenosine deaminase levels in serum and

ur

synovial fluid between patients with rheumatoid arthritis and osteoarthritis., Int. J. Clin.

Jo

Exp. Med. 5 (2012) 195–200.

[229] Y. Nakamachi, M. Koshiba, T. Nakazawa, S. Hatachi, R. Saura, M. Kurosaka, H. Kusaka, S. Kumagai, Specific increase in enzymatic activity of adenosine deaminase 1 in rheumatoid synovial fibroblasts, Arthritis Rheum. 48 (2003) 668–674. doi:10.1002/art.10956. [230] A. Sasidharan, S. Kumar, J.P. John, M. Philip, S. Subramanian, S. Jain, B.M. Kutty, Elevated serum adenosine deaminase levels in neuroleptic-naïve patients with recent-onset schizophrenia, Asian J. Psychiatr. 29 (2017) 13–15. doi:10.1016/j.ajp.2017.03.034.

48

Journal Pre-proof [231] S. Taysi, M.F. Polat, R.A. Sari, E. Bakan, Serum adenosine deaminase and cytidine deaminase activities in patients with systemic lupus erythematosus, Clin Chem Lab Med. 40 (2002) 493–495. doi:10.1515/CCLM.2002.085 [doi]. [232] M. Stancíková, J. Lukác, R. Istok, G. Cristalli, J. Rovensky, Serum adenosine deaminase activity and its isoenzyme pattern in patients with systemic lupus erythematosus, Clin.

of

Exp. Rheumatol. 16 (1998) 583–586.

ro

[233] I. Durak, N. Örmeci, Ö. Akyol, O. Canbolat, M. Kavutçu, M. Bülbül, Adenosine

-p

deaminase, 5′-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis,

re

Dig. Dis. Sci. 39 (1994) 721–728. doi:10.1007/BF02087413.

lP

[234] K.S. Dasmahapatra, H.Z. Hill, A. Dasmahapatra, S. Suarez, Evaluation of adenosine

na

deaminase activity in patients with head and neck cancer., J. Surg. Res. 40 (1986) 368–73.

ur

[235] I. Durak, C.Ü. Işik, O. Canbolat, Ö. Akyol, M. Kavutçu, Adenosine deaminase, 5′ nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous

Jo

and noncancerous human laryngeal tissues, Free Radic. Biol. Med. 15 (1993) 681–684. doi:10.1016/0891-5849(93)90174-S. [236] V. Battisti, L.D.K. Maders, M.D. Bagatini, I.E. Battisti, L.P. Bellé, K.F. Santos, P.A. Maldonado, G.R. Thomé, M.R.C. Schetinger, V.M. Morsch, Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: Influence of Gleason score, treatment and bone metastasis, Biomed. Pharmacother. 67 (2013) 203–208. doi:10.1016/j.biopha.2012.12.004.

49

Journal Pre-proof [237] V.O. Iaroshenko, D. Ostrovskyi, A. Petrosyan, S. Mkrtchyan, A. Villinger, P. Langer, Synthesis of Fluorinated Purine and 1-Deazapurine Glycosides as Potential Inhibitors of Adenosine Deaminase, J. Org. Chem. 76 (2011) 2899–2903. doi:10.1021/jo102579g. [238] S. Alunni, M. Orrù, L. Ottavi, A study on the inhibition of adenosine deaminase, J. Enzyme Inhib. Med. Chem. 23 (2008) 182–189. doi:10.1080/14756360701475233.

of

[239] P.C. Tyler, E.A. Taylor, R.F.G. Fröhlich, V.L. Schramm, Synthesis of 5′-methylthio

ro

coformycins: Specific inhibitors for malarial adenosine deaminase, J. Am. Chem. Soc. 129

-p

(2007) 6872–9. doi:10.1021/ja0708363.

re

[240] G. Ataie, S. Safarian, A. Divsalar, A.A. Saboury, A.A. Moosavi-Movahedi, B. Ranjbar, G. Cristalli, S. Mardanian, Kinetic and structural analysis of the inhibition of adenosine

lP

deaminase by acetaminophen, J. Enzyme Inhib. Med. Chem. 19 (2004) 71–8.

na

doi:10.1080/14756360310001632741.

ur

[241] G. Ataie, S. Bagheri, A. Divsalar, A.A. Saboury, S. Safarian, S. Namaki, A.A. MoosaviMovahedi, A Kinetic Comparison on the Inhibition of Adenosine Deaminase by Purine

Jo

Drugs, Iran. J. Pharm. Res. 6 (2007) 43–50. [242] A. Łupicka-Słowik, M. Psurski, R. Grzywa, K. Bobrek, P. Smok, M. Walczak, A. Gaweł, T. Stefaniak, J. Oleksyszyn, M. Sieńczyk, Development of Adenosine Deaminase-Specific IgY Antibodies: Diagnostic and Inhibitory Application, Appl. Biochem. Biotechnol. 184 (2018) 1358–1374. doi:10.1007/s12010-017-2626-x. [243] A. Reayi, R.S. Hosmane, Inhibitors of adenosine deaminase: continued studies of structure-activity relationships in analogues of coformycin., Nucleosides. Nucleotides

50

Journal Pre-proof Nucleic Acids. 23 (2004) 263–71. [244] D. Ajloo, A.A. Saboury, N. Haghi-Asli, G. Ataei-Jafarai, A.A. Moosavi-Movahedi, M. Ahmadi, K. Mahnam, S. Namaki, Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac, J. Enzyme Inhib. Med. Chem. 22 (2007) 395–406. doi:10.1080/14756360701229085.

of

[245] T. Tite, N. Lougiakis, V. Myrianthopoulos, P. Marakos, E. Mikros, N. Pouli, R. Tenta, E.

ro

Fragopoulou, T. Nomikos, Design and synthesis of new C-nucleosides as potential

-p

adenosine deaminase inhibitors, Tetrahedron. 66 (2010) 9620–9628.

re

doi:10.1016/j.tet.2010.10.005.

[246] A.A. Saboury, A. Divsalar, G. Ataie, M. Amanlou, A.A. Moosavi-Movahedi, G.H.

lP

Hakimelahi, Inhibition study of adenosine deaminase by caffeine using spectroscopy and

na

isothermal titration calorimetry, Acta Biochim. Pol. 50 (2003) 849–855. doi:035003849.

ur

[247] M. Amanlou, A. Saboury, R. Bazl, M.R. Ganjali, S. Sheibani, Adenosine deaminase activity modulation by some street drug: molecular docking simulation and experimental

Jo

investigation., Daru. 22 (2014) 1–8. doi:10.1186/2008-2231-22-42. [248] S.R. Kandalkar, P.A. Ramaiah, M. Joshi, A. Wavhal, Y. Waman, A.A. Raje, A. Tambe, S. Ansari, S. De, V.P. Palle, K.A. Mookhtiar, A.M. Deshpande, D.A. Barawkar, Modifications of flexible nonyl chain and nucleobase head group of (+)-erythro-9-(2′shydroxy-3′s-nonyl)adenine [(+)-EHNA] as adenosine deaminase inhibitors, Bioorganic Med. Chem. 25 (2017) 5799–5819. doi:10.1016/j.bmc.2017.09.015. [249] M. Kuno, N. Seki, S. Tsujimoto, I. Nakanishi, T. Kinoshita, K. Nakamura, T. Terasaka, N.

51

Journal Pre-proof Nishio, A. Sato, T. Fujii, Anti-inflammatory activity of non-nucleoside adenosine deaminase inhibitor FR234938, Eur. J. Pharmacol. 534 (2006) 241–249. doi:10.1016/j.ejphar.2006.01.042. [250] K.G. Arun, C.S. Sharanya, P.M. Sandeep, C. Sadasivan, Inhibitory activity of hibifolin on adenosine deaminase- experimental and molecular modeling study, Comput. Biol. Chem.

of

64 (2016) 353–358. doi:10.1016/j.compbiolchem.2016.08.005.

ro

[251] G. Lee, S.S. Lee, K.Y. Kay, D.W. Kim, S. Choi, H.K. Jun, Isolation and characterization

-p

of a novel adenosine deaminase inhibitor, IADA-7, from Bacillus sp. J-89, J. Enzyme

re

Inhib. Med. Chem. 24 (2009) 59–64. doi:10.1080/14756360801906863. [252] A.A. Saboury, A. Divsalar, G. Ataie, A.A. Moosavi-Movahedi, M. Housaindokht, G.H.

lP

Hakimelahi, A Product inhibition study on adenosine deaminase by spectroscopy and

na

calorimetry, J. Biochem. Mol. Biol. 35 (2002) 302–305.

ur

[253] T. Terasaka, K. Tsuji, T. Kato, I. Nakanishi, T. Kinoshita, Y. Kato, M. Kuno, T. Inoue, K. Tanaka, K. Nakamura, Rational design of non-nucleoside, potent, and orally bioavailable

Jo

adenosine deaminase inhibitors: Predicting enzyme conformational change and metabolism, J. Med. Chem. 48 (2005) 4750–4753. doi:10.1021/jm050413g. [254] T. Terasaka, T. Kinoshita, M. Kuno, I. Nakanishi, A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization., J. Am. Chem. Soc. 126 (2004) 34–5. doi:10.1021/ja038606l. [255] A.B. Gurung, A. Bhattacharjee, Structure based virtual screening identifies Pranlukast as a potential inhibitor against Plasmodium falciparum Adenosine Deaminase enzyme, Gene

52

Journal Pre-proof Reports. 6 (2017) 54–66. doi:10.1016/j.genrep.2016.12.003. [256] I. Gillerman, B. Fischer, Investigations into the origin of the molecular recognition of several adenosine deaminase inhibitors, J. Med. Chem. 54 (2011) 107–121. doi:10.1021/jm101286g. [257] S.C. Zimmermann, J.M. Sadler, P.I. O’Daniel, N.T. Kim, K.L. Seley-Radtke, “Reverse”

of

Carbocyclic Fleximers: Synthesis of a New Class of Adenosine Deaminase Inhibitors,

ro

Nucleosides, Nucleotides and Nucleic Acids. 32 (2013) 137–154.

-p

doi:10.1080/15257770.2013.771187.

re

[258] A.A. Saboury, S. Bagheri, G. Ataie, A.A. Moosavi-Movahedi, G.H. Hakimelahi, G. Cristalli, S. Mardanian, Kinetic and thermodynamic study on the inhibition of adenosine

lP

deaminase by theobromine, Asian J. Chem. 17 (2005) 233–239.

na

[259] A.A. Saboury, S. Bagheri, G. Ataie, M. Amanlou, A.A. Moosavi-Movahedi, G.H.

ur

Hakimelahi, G. Cristalli, S. Namaki, Binding properties of adenosine deaminase interacted with theophylline., Chem. Pharm. Bull. (Tokyo). 52 (2004) 1179–82.

Jo

doi:10.1248/cpb.52.1179.

[260] A.J. Akinyemi, N. Onyebueke, O.A. Faboya, S.A. Onikanni, A. Fadaka, I. Olayide, Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney, J. Food Drug Anal. 25 (2017) 438–446. doi:10.1016/j.jfda.2016.06.004. [261] H. Ni, Y.-H. Li, R.-L. Hao, H. Li, S.-Q. Hu, H.-H. Li, Identification of adenosine deaminase inhibitors from Tofu wastewater and litchi peel and their synergistic anticancer

53

Journal Pre-proof and antibacterial activities with cordycepin, Int. J. Food Sci. Technol. 51 (2016) 1168– 1176. doi:10.1111/ijfs.13064. [262] Z.E. Durak, H. Kocaoğlu, Echinacea Inhibits Adenosine Deaminase Enzyme in Cancerous Human Gastric Tissue, J. Carcinog. Mutagen. 6 (2015) 1000246. doi:10.4172/2157-2518.1000246.

of

[263] K.G. Arun, C.S. Sharanya, C. Sadasivan, Computational and experimental validation of

ro

morin as adenosine deaminase inhibitor, J. Recept. Signal Transduct. 38 (2018) 240–245.

-p

doi:10.1080/10799893.2018.1476543.

re

[264] I. Durak, H. Biri, E. Devrim, S. Sözen, A. Avci, Aqueous extract of Urtica dioica makes significant inhibition on adenosine deaminase activity in prostate tissue from patients with

Jo

ur

na

lP

prostate cancer., Cancer Biol. Ther. 3 (2004) 855–857. doi:10.4161/cbt.3.9.1038.

54

Journal Pre-proof Table 1 The increase of ADA activity in different diseases Disease or disorder Acquired syndrome

immune

The examined tissue or fluid deficiency Serum

References [46]

Serum

[97,182]

Appendicitis

Serum

[183]

Atherosclerosis

Serum

Autoimmune hepatitis

Serum

Behçet's disease

Serum, Plasma

Bladder cancer

Serum

Bladder cancer

Bladder tissues

ro

-p

re

lP

[57] [100] [92,93,184] [185] [102,186]

Serum

[187,188]

Breast tissues

[98,189]

na

Breast cancer Breast cancer

of

Acute lymphoblastic leukemia

[190]

Chronic granulomatous disease

Serum

[191]

Colorectal cancer

Colorectal tissues

[103,192]

Crimean–Congo hemorrhagic fever

Serum

[193]

Diabetes

Macrophages, Serum

[194–202]

Jo

ur

Chronic ENT (ear, nose, throat) Serum infections

55

Journal Pre-proof Table 1 The increase of ADA activity in different diseases, continued The examined tissue or fluid

References

Gastric cancer

Gastric tissues

[203]

Gastrointestinal diseases

Serum

[60,204–206]

Head and neck carcinoma

Serum

[207]

Head and neck squamous cell cancer- Early stages

Serum

Hepatitis B

Serum

Human immunodeficiency virus infection

Serum, Plasma

Hyper IgM

Serum

lP

re

-p

ro

of

Disease or disorder

Hyperthyroid

[207]

[208] [46,105–109]

[191]

Plasma

[209]

Serum

[191]

Serum

[210]

Serum

[191]

Pleural effusion, Sputum, Serum

[94,211–213]

Male infertility

Plasma

[214]

Memory disorders (in rats)

cerebral cortex

[215]

Multiple sclerosis

Serum

[216]

Myasthenia gravis

Serum

[85,86]

Obesity

Saliva

[217]

Oral squamous cell carcinoma

Serum

[95]

na

IgA deficiency

ur

Laryngeal cancer

Lung diseases

Jo

Leukocyte adhesion deficiency

56

Journal Pre-proof Serum

[84,218]

Jo

ur

na

lP

re

-p

ro

of

Pancreatic diseases

57

Journal Pre-proof Table 1 The increase of ADA activity in different diseases, continued The examined tissue or fluid

References

Panic disorder

Serum

[219]

Parkinson’s disease

Serum

[220]

Pseudoexfoliation syndrome

Serum

[221]

Psoriasis

Serum

Renal cell carcinoma

Serum

Rheumatoid arthritis

Serum, synovial fluid , fibroblast-like synoviocytes, pleural effusion

Schizophrenia

Serum

Systemic inflammatory response syndrome

Serum

of

Disease or disorder

na

lP

re

-p

ro

[222–224] [96] [87–89,225–229]

[230] [145]

Serum

[90,91,231,232]

Wiskott–Aldrich syndrome

Serum

[191]

Jo

ur

Systemic lupus erythematosus

58

Journal Pre-proof Table 2 The decrease of ADA activity in some cancers The examined tissue or fluid

References

Gastric cancer

Gastric juice

[233]

Head and neck squamous cell cancer-Advanced

Lymphocytes, Serum

[207,234]

Laryngeal cancer-squamous cell carcinomas

Laryngeal tissues

[235]

Prostate cancer

Serum

Jo

ur

na

lP

re

-p

ro

of

Disease or disorder

59

[236]

Journal Pre-proof Table 3 The synthetic compounds inhibiting ADA activity Conditions of ADA-inhibition References measurement

1-deazapurine glycosides

in vitro

[237]

2-aminopurine

in vitro

[238]

4-aminopyridine

in vitro

[238]

4-aminopyrimidine

in vitro

4-hydroxypyridine

in vitro

5 '-methylthio coformycins

in vitro

Acetaminophen

in vitro

[240]

in vitro

[241]

re

-p

ro

of

Compound

Adenine

lP

Acyclovir

[238] [238] [239]

in vitro

[238]

in vitro

[242]

in vitro

[241]

Analogues of coformycin

in vitro

[243]

Aspirin

in vitro

[244]

C-nucleosides

in vitro

[245]

Caffeine

in vitro

[246]

Cocain

in vitro

[247]

Diclofenac

in vitro

[244]

EHNA

in rat tissue

[138]

EHNA analogues

in vitro

[248]

ur

Jo

Allopurinol

na

Adenosine deaminase specific IgY Antibodies

60

Journal Pre-proof Table 3 The synthetic compounds inhibiting ADA activity, continued Conditions of ADA-inhibition References measurement

Ethylmorphine

in vitro

[247]

Fluorinated Purine

in vitro

[237]

FR234938

in vitro

[249]

Ge-132

in vitro

Hibifolin

in vitro

Homatropine

in vitro

IADA-7

in vitro

[251]

in vitro

[238,252]

re

-p

ro

of

Compound

lP

Inosine

[250] [247]

in rat (tissues) in human (serum and synovial fluid) in vitro

[176,228]

in vitro

[253,254]

in vitro

[238]

in vitro

[255]

Purine

in vitro

[238]

Purine-riboside analogues

in vitro

[256]

Reverse carbocyclic fleximers

in vitro

[257]

Thebaine

in vitro

[247]

Theobromin

in vitro

[258]

Theophylline

in vitro

[259]

Morphine

Pranlukast

Jo

Phenylhydrazine

ur

Non-nucleoside inhibitor

na

Methotrexate

[177]

61

[247]

Journal Pre-proof Table 4 The natural compounds inhibiting ADA activity Compound

Conditions of ADA-inhibition References measurement

Allium sativum

[166,168,169,171]

Curcumin

in vitro in patients in rat

Cyanidin-3-rutinoside

in vitro

[261]

Echinacea

in cancerous human gastric tissue

[262]

Genistein

in vitro

[261]

Metabolite from aspergillus niger (endophytic fungi)

in vitro

[6]

of

ro

-p

re in human and animal models

[160,162–165]

in human prostate cancer tissues

[157]

in human prostate cancer tissues

[264]

Jo

ur

na

Syzygium cumini

Urtica dioica

[263]

in vitro

lP

Morin (a bioactive flavonoid)

Tomato juice

[260]

62

Journal Pre-proof Fig. 1. Schematic figure of ADA1 activity and localization.

Jo

ur

na

lP

re

-p

ro

of

Fig. 2. Schematic figure of ADA1 interactions with adenosine receptors.

63

Journal Pre-proof

Jo

ur

na

lP

re

-p

ro

of

Bagheri et al. /Fig.1 /International Journal of Biological Macromolecules

64

Journal Pre-proof

Jo

ur

na

lP

re

-p

ro

of

Bagheri et al. /Fig.2 /International Journal of Biological Macromolecules

65

Figure 1

Figure 2