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Synthesis and characterization of zinc naphthalocyanine derivative with potential application in photodynamic therapy
Abstracts / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375
dismutase (MnSOD) overexpressed RGK cells RGK-MnSOD. Since MnSOD is expressed in mitochondria, mitROS can be specifically scavenged. In this study, we have succeeded to demonstrate that cancer specific high mitROS concentration plays an important role for the acceleration of PEPT1 expression and ALA incorporation. http://dx.doi.org/10.1016/j.pdpdt.2015.07.140 Enhancement of photodynamic therapy effects with mitochondrial reactive oxygen species Ito 1 , Hirofumi Matsui 1 , Masato Tamura 1 , Tsuyoshi Kaneko 1 , Ichinosuke Hyodo 1 , Hiroko P. Indo 2 , Hideyuki J. Majima 2 1
Faculty of Medicine, University of Tsukuba, Japan 2 Graduate School of Medical and Dental Sciences, Kagoshima University, Japan Photodynamic therapy (PDT) using porphyrin compounds is one of effective cancer treatments and often used for senior clinically. This therapy is based on the characteristics that porphyrin used to be accumulated into cancer cells. We previously reported this phenomenon attributed a membrane transporter, heme carrier protein 1 (HCP1), which has a role to transport heme into cells. However, the expression mechanism of the protein has not been confirmed. It is reported that HCP1 expression is related to hypoxic condition where mitochondrial reactive oxygen species (mitROS) had often been generated. Therefore mitROS may play an important role for HCP1 expression. In this study, we have clarified the relation between the HCP1 expression and mitROS by use of rat gastric mucosal cells RGM1, its cancer-like mutated cells RGK1, and manganese superoxide dismutase (MnSOD) overexpressed RGK cells RGK-MnSOD. Since MnSOD is specifically expressed in a mitochondrion, it can scavenge mitROS directly. The amounts of mitROS in RGK1 were larger than that in RGK-MnSOD. Moreover, HCP1 expression level and PDT effect after exposing porpyrin of cancer cell were also highest in these cells. According to these results, mitROS were most likely to accelerate HCP1 expression and enhance PDT effect. http://dx.doi.org/10.1016/j.pdpdt.2015.07.141 Synthesis and characterization of novel symmetrical and asymmetrical carboxyphthalocyanines with potential application in photodynamic therapy Francisco B. do Nascimento, Anderson O. Ribeiro Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil Tetracarboxyphthalocyanines were synthesized modifying the phthalonitrile precursors with lactic and glycolic acids. The synthetic route starts with the selective esterification of ␣-hydroxycarboxylic acids catalyzed by boric acid. Afterward, the isolated esterified compounds were reacted with 4-nitrophthalonitrile to produce the phthalonitrile precursors. Symmetrical carboxyphthalocyanines were synthesized by cyclotetramerization of phthalonitrile derivatives in the presence of a few drops DBU as a strong base and anhydrous Zn(CH3 COO)2 at reflux temperature under a nitrogen atmosphere in n-pentanol. The asymmetrical carboxyphthalocyanines (3:1) were synthesized by Kobayashi ring expansion of boron subphthalocyanines derivatives. The synthetic route used to obtain the precursors and the carboxyphthalocyanines analogs was very efficient, seeing that all
361
compounds were isolated with good yields. 1 H NMR spectroscopy, infrared absorption and mass analysis were used to characterize the structure of all compounds. UV–vis and fluorescence spectra were recorded in DMSO for all carboxyphthalocyanines to determine the quantum yields of fluorescence and photodegradation. The singlet-oxygen production was obtained by indirect method, using DBPF as chemical quencher. All carboxyphthalocyanines showed interesting photophysical and photochemical properties to be considered as potential photosensitizer for PDT application. Further studies of this system are in progress. http://dx.doi.org/10.1016/j.pdpdt.2015.07.142 Synthesis and characterization of zinc naphthalocyanine derivative with potential application in photodynamic therapy Thalita Ferreira Menegassi de Souza, Anderson Orzari Ribeiro Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil Naphthalocyanine (Nc) is a derivative of phthalocyanine (Pc), which possesses four extra benzene rings condensed to the periphery of the Pc macrocycle. This produces a bathochromic shift to the maxima absorption of the Q-band sensitizing to near infrared region (700–900 nm) which provides advantages for the use of Photodynamic Therapy. The precursor of Nc derivative, tert-butyl-dicyanobenzene, was synthesized by allylic bromination of tert-butyl-o-xylene with N-bromosuccinimide at 125W Hg lamp for 6 h followed by reaction with fumaronitrile. The tert-butylphthalocyanine and tert-butylnaphthalocyanine were synthesized in pentanol with zinc acetate and DBU as catalyst. The UV/vis and fluorescence spectra show characteristic absorptions in the Q-band and fluorescence emission around 680 nm to Pc and 770 nm to Nc derivative, the red shift by 90 nm was due to the extended conjugation. The singlet oxygen production was evaluated using DPBF as a suppressor. For photobleaching studies, the solution of compound was irradiated at 650 nm for 5 min. Compared to Pc, Nc have smaller singlet oxygen quantum yield and largest photobleaching. However, all compounds show a substantial aggregation tendency in DMSO:water solution and the degree of association depends largely on the additional interactions due to the substituents. Further studies of this system are in progress. http://dx.doi.org/10.1016/j.pdpdt.2015.07.143 Toxic and phototoxic effects of a new ruthenium phthalocyanine on human breast cancer cells (MCF-7) Thaiza Ferreira Menegassi de Souza, Anderson Orzari Ribeiro, Giselle Cerchiaro Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil Photodynamic therapy (PDT) is a treatment for cancer based on the interaction of a photosensitizer, light and oxygen resulting in the formation of reactive species. In this work, we analyzed the interaction of a new ruthenium phthalocyanine on human breast cancer cells (MCF-7) through the test with Bromide Thiazolyl Blue Tetrazolium – MTT. The cells were incubated in Roswell Park Memorial Institute (RPMI)-1640 medium (Sigma) supplemented with 10% fetal bovine serum (Gibco) in 85% humidified atmosphere at 37 ◦ C and 5% CO2. Cells were plated in 96-well plates and after
dismutase (MnSOD) overexpressed RGK cells RGK-MnSOD. Since MnSOD is expressed in mitochondria, mitROS can be specifically scavenged. In this study, we have succeeded to demonstrate that cancer specific high mitROS concentration plays an important role for the acceleration of PEPT1 expression and ALA incorporation. http://dx.doi.org/10.1016/j.pdpdt.2015.07.140 Enhancement of photodynamic therapy effects with mitochondrial reactive oxygen species Ito 1 , Hirofumi Matsui 1 , Masato Tamura 1 , Tsuyoshi Kaneko 1 , Ichinosuke Hyodo 1 , Hiroko P. Indo 2 , Hideyuki J. Majima 2 1
Faculty of Medicine, University of Tsukuba, Japan 2 Graduate School of Medical and Dental Sciences, Kagoshima University, Japan Photodynamic therapy (PDT) using porphyrin compounds is one of effective cancer treatments and often used for senior clinically. This therapy is based on the characteristics that porphyrin used to be accumulated into cancer cells. We previously reported this phenomenon attributed a membrane transporter, heme carrier protein 1 (HCP1), which has a role to transport heme into cells. However, the expression mechanism of the protein has not been confirmed. It is reported that HCP1 expression is related to hypoxic condition where mitochondrial reactive oxygen species (mitROS) had often been generated. Therefore mitROS may play an important role for HCP1 expression. In this study, we have clarified the relation between the HCP1 expression and mitROS by use of rat gastric mucosal cells RGM1, its cancer-like mutated cells RGK1, and manganese superoxide dismutase (MnSOD) overexpressed RGK cells RGK-MnSOD. Since MnSOD is specifically expressed in a mitochondrion, it can scavenge mitROS directly. The amounts of mitROS in RGK1 were larger than that in RGK-MnSOD. Moreover, HCP1 expression level and PDT effect after exposing porpyrin of cancer cell were also highest in these cells. According to these results, mitROS were most likely to accelerate HCP1 expression and enhance PDT effect. http://dx.doi.org/10.1016/j.pdpdt.2015.07.141 Synthesis and characterization of novel symmetrical and asymmetrical carboxyphthalocyanines with potential application in photodynamic therapy Francisco B. do Nascimento, Anderson O. Ribeiro Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil Tetracarboxyphthalocyanines were synthesized modifying the phthalonitrile precursors with lactic and glycolic acids. The synthetic route starts with the selective esterification of ␣-hydroxycarboxylic acids catalyzed by boric acid. Afterward, the isolated esterified compounds were reacted with 4-nitrophthalonitrile to produce the phthalonitrile precursors. Symmetrical carboxyphthalocyanines were synthesized by cyclotetramerization of phthalonitrile derivatives in the presence of a few drops DBU as a strong base and anhydrous Zn(CH3 COO)2 at reflux temperature under a nitrogen atmosphere in n-pentanol. The asymmetrical carboxyphthalocyanines (3:1) were synthesized by Kobayashi ring expansion of boron subphthalocyanines derivatives. The synthetic route used to obtain the precursors and the carboxyphthalocyanines analogs was very efficient, seeing that all
361
compounds were isolated with good yields. 1 H NMR spectroscopy, infrared absorption and mass analysis were used to characterize the structure of all compounds. UV–vis and fluorescence spectra were recorded in DMSO for all carboxyphthalocyanines to determine the quantum yields of fluorescence and photodegradation. The singlet-oxygen production was obtained by indirect method, using DBPF as chemical quencher. All carboxyphthalocyanines showed interesting photophysical and photochemical properties to be considered as potential photosensitizer for PDT application. Further studies of this system are in progress. http://dx.doi.org/10.1016/j.pdpdt.2015.07.142 Synthesis and characterization of zinc naphthalocyanine derivative with potential application in photodynamic therapy Thalita Ferreira Menegassi de Souza, Anderson Orzari Ribeiro Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil Naphthalocyanine (Nc) is a derivative of phthalocyanine (Pc), which possesses four extra benzene rings condensed to the periphery of the Pc macrocycle. This produces a bathochromic shift to the maxima absorption of the Q-band sensitizing to near infrared region (700–900 nm) which provides advantages for the use of Photodynamic Therapy. The precursor of Nc derivative, tert-butyl-dicyanobenzene, was synthesized by allylic bromination of tert-butyl-o-xylene with N-bromosuccinimide at 125W Hg lamp for 6 h followed by reaction with fumaronitrile. The tert-butylphthalocyanine and tert-butylnaphthalocyanine were synthesized in pentanol with zinc acetate and DBU as catalyst. The UV/vis and fluorescence spectra show characteristic absorptions in the Q-band and fluorescence emission around 680 nm to Pc and 770 nm to Nc derivative, the red shift by 90 nm was due to the extended conjugation. The singlet oxygen production was evaluated using DPBF as a suppressor. For photobleaching studies, the solution of compound was irradiated at 650 nm for 5 min. Compared to Pc, Nc have smaller singlet oxygen quantum yield and largest photobleaching. However, all compounds show a substantial aggregation tendency in DMSO:water solution and the degree of association depends largely on the additional interactions due to the substituents. Further studies of this system are in progress. http://dx.doi.org/10.1016/j.pdpdt.2015.07.143 Toxic and phototoxic effects of a new ruthenium phthalocyanine on human breast cancer cells (MCF-7) Thaiza Ferreira Menegassi de Souza, Anderson Orzari Ribeiro, Giselle Cerchiaro Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil Photodynamic therapy (PDT) is a treatment for cancer based on the interaction of a photosensitizer, light and oxygen resulting in the formation of reactive species. In this work, we analyzed the interaction of a new ruthenium phthalocyanine on human breast cancer cells (MCF-7) through the test with Bromide Thiazolyl Blue Tetrazolium – MTT. The cells were incubated in Roswell Park Memorial Institute (RPMI)-1640 medium (Sigma) supplemented with 10% fetal bovine serum (Gibco) in 85% humidified atmosphere at 37 ◦ C and 5% CO2. Cells were plated in 96-well plates and after