New environmentally-friendly antimicrobials and biocides from Andean and Mexican biodiversity

Environmental Research 142 (2015) 549–562

Contents lists available at ScienceDirect

Environmental Research journal homepage: www.elsevier.com/locate/envres

Review article

New environmentally-friendly antimicrobials and biocides from Andean and Mexican biodiversity Carlos L. Cespedes a,n, Julio Alarcon b, Pedro M. Aqueveque c, Tatiana Lobo d, Julio Becerra b, Cristian Balbontin a, Jose G. Avila e, Isao Kubo f, David S. Seigler g a Phytochemical-Ecology, Grupo de Investigación Quimica y Biotecnología de Productos Naturales Bioactivos, Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad del Bio Bio, Chillan, Chile b Synthesis/Biotransformation of Natural Products Labs, Grupo de Investigación Quimica y Biotecnología de Productos Naturales Bioactivos, Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad del Bio Bio, Chillan, Chile c Laboratorio de Microbiología y Micología Aplicada, Departamento de Agroindustrias, Facultad de Ingeniería Agrícola, Universidad de Concepción, Chillan, Chile d Escuela de Quimica, Facultad de Ciencias, Universidad Nacional de Colombia sede Medellin, Colombia e Laboratorio de Fitoquimica, Unidad UBIPRO, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla, Mexico DF, Mexico f ESPM Departmenty, University of California at Berkeley, CA, USA g Department of Plant Biology, Herbarium, University of Illinois at Urbana-Champaign, IL, USA

art ic l e i nf o

a b s t r a c t

Article history: Received 10 March 2015 Received in revised form 6 August 2015 Accepted 6 August 2015

Persistent application of pesticides often leads to accumulation in the environment and to the development of resistance in various organisms. These chemicals frequently degrade slowly and have the potential to bio-accumulate across the food chain and in top predators. Cancer and neuronal damage at genomic and proteomic levels have been linked to exposure to pesticides in humans. These negative effects encourage search for new sources of biopesticides that are more “environmentally-friendly” to the environment and human health. Many plant or fungal compounds have significant biological activity associated with the presence of secondary metabolites. Plant biotechnology and new molecular methods offer ways to understand regulation and to improve production of secondary metabolites of interest. Naturally occurring crop protection chemicals offer new approaches for pest management by providing new sources of biologically active natural products with biodegradability, low mammalian toxicity and environmentally-friendly qualities. Latin America is one of the world’s most biodiverse regions and provide a previously unsuspected reservoir of new and potentially useful molecules. Phytochemicals from a number of families of plants and fungi from the southern Andes and from Mexico have now been evaluated. Andean basidiomycetes are also a great source of scientifically new compounds that are interesting and potentially useful. Use of biopesticides is an important component of integrated pest management (IPM) and can improve the risks and benefits of production of many crops all over the world. & 2015 Elsevier Inc. All rights reserved.

Keywords: Biopesticides Environmentally-friendly biopesticides Antifeedant Insect growth regulators Insecticidal Antibacterial Antifungal activity Secondary metabolites Phytopathogens Insect pest control Biological activity.

1. Introduction Although application of pesticides is necessary for modern agriculture, overuse often leads to ecological and environmental problems. Many modern pesticides are biodegradable, but others are persistent in the environment and contribute to the development of resistance in various organisms. In fact, many are easily degradable and readily metabolized, even though they are still

n Correspondence to: University of Bio Bio, Faculty of Sciences, Basic Sciences Department, Andres Bello Avenue s/n, CP 3780000 Chillan, Chile. E-mail address: [email protected] (C.L. Cespedes).

http://dx.doi.org/10.1016/j.envres.2015.08.004 0013-9351/& 2015 Elsevier Inc. All rights reserved.

responsible for environment problems. Although many pest organisms are controlled, many beneficial insects and microorganisms are eliminated. The effects of organophosphates, glyphosate, paraquat, diquat, maneb, and other ethylene bis-dithiocarbamates are complex (Alavanja et al., 2004; Lee et al., 2008; Hancock et al., 2008). Some of these pesticides degrade slowly and have the potential to bio-accumulate across the food chain and in top predators through consumption of contaminated biota (Bjermo et al., 2013; Frouin et al., 2013). In addition to those applied in agriculture, other persistent organic compounds arise from waste incineration, industrial chemical processes, unregulated disposal of textiles, building materials and burning of waste and vegetation (Antunes et al., 2012; Liu et al., 2013; Evenset et al., 2007).

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Inorganic materials such as obsolete electronic waste (e-waste) also contribute to this problem. Once released, these substances tend to accumulate in soils and sediments for a long period of time and are subject to partitioning, degradation and transport processes. In addition to ecological effects on the environment, a number of these pesticides have been shown to have potential effects on human health. Cancer and neuronal damage at genomic and proteomic levels have been linked to exposure to pesticides (Whitehead et al., 2015; Margni et al., 2002; Snell et al., 2003). Numerous studies have been conducted to investigate the potential neuroprotective action of natural products in neurotoxin-based models of Parkinson’s disease (Sudati et al., 2013). Although the association between pesticide exposure and Parkinson´s disease (PD) has been established (Hancock et al., 2008; Lee et al., 2008; Rhodes et al., 2013), the specific mechanisms involved in the damage to dopaminergic function have not yet been fully elucidated. One proposed mechanism suggests that pesticides could be the cause of neurodegenerative diseases through the inhibition of mitochondrial function. The structure of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) is similar to that of paraquat. MPTP is an agent known to cause damage to mitochondrial complex I (Le Couteur et al., 1999) and to induce the destruction of nigral dopaminergic neurons with a consequent neurobehavioral syndrome in mice (Thiruchelvam et al., 2000). Recently an interesting contribution to the understanding of this phenomenon was made by Qi et al. (2014) who, through mathematical simulations, have shown that both paraquat and rotenone may affect all fluxes associated with dopamine compartmentalization and its breakdown metabolites. In other studies, oxidative stress has been shown to play a central role in Parkinson’s disease; for example, Garrido et al. (2011) showed that the application of pesticides could induce Lewy body formation, dopaminergic neurodegeneration, decrease in striatal dopamine levels and disturbances in GSH homeostasis. In addition, changes in the expression pattern of genes associated with the development of PD as tyrosine hydroxylase, alpha-synuclein, Parkin, PINK1 or DJ-1, have been correlated with exposure to rotenone and MPTP (Rajput and Rajput, 2007). The negative effects of persistent organic pesticides are drivers in the search of new sources of biopesticides that are more “environmentally-friendly” to the environment and human health. Biopesticides and biocides are derived from such natural materials as animals, plants, fungi, bacteria, and certain minerals (EPA) (http://www.epa.gov/pesticides/about/types.htm). Since the beginning of civilization, substances obtained from botanical and fungal sources have been employed for agriculture, medicinal, or other cultural uses. Plants and fungi from many families produce a broad spectrum of natural products known as secondary metabolites (SM). These organisms still represent a large source of novel active biological compounds with insecticidal, nematicidal, herbicidal, antiviral, antifungal, antifeedant and antibacterial activities (Cantrell et al., 2012). Many plant or fungal compounds have significant biological activity associated with the presence of alkaloids, mono-, iridoid monoterpenes, sesqui-, sesquiterpene lactones, di- and triterpenes, flavonoids, naphthoquinones, anthroquinones, coumarins, phenylpropanoids, flavonoids, and other types of phenolics (Rios and Recio, 2005; Svetaz et al., 2013). As a rule these substances are more degradable than many persistent pesticides; they may eliminate or significantly reduce the risk of adverse ecological effects and of soil and groundwater contamination (Seigler, 1998). Of course, compounds or extracts from plants or fungi will ultimately have to be evaluated for safety, efficaciousness, and a set of enviornmental problems in their own right. Just because they are “natural” does not mean that their use will be completely free from problems!

Many phytochemical isolations are biodirected in order to find new botanical and mycological biocides rather than simply to isolate compounds with new chemical structures. Botanically- and fungally-derived compounds that exhibit resistance to attack by pests may serve as agrochemicals by taking advantage of their antifeedant, insecticidal, fungicidal, nematicidal, molluscicidal, repellent, and herbicidal activity. Other SM have toxicity toward weeds and bacterial and fungal phytopathogens. In many instances, SM from fungi have greater potency as biocides than those isolated from higher plants suggesting that they are a promising, but inadequately explored, source of bioactive compounds. Substances from lichens, mosses, liverworts, and ferns have been insufficiently examined, but the literature available suggests that they also may provide many new active compounds (Aqueveque et al., 2005; 2006; 2010a,b). The impact of plant natural products (phytochemicals) on human health, the food industry and crop production is increasingly recognized (Tajkarimi et al., 2010). Many plants and fungi have served as medicines for humans. Natural products have the ability to inhibit or modify the activity of many enzymes including tyrosinase, acetylcholinesterase, and melanin oxidase, and may play a role in health promoting activities (Schinella et al., 2002; Arrebola et al., 2015; He et al., 2015). Plant, fungal and bacterial natural products can be used as drugs against many diseases such as cancer, neuro-degenerative diseases, bacterial–fungal pathogens, and inflammation among others. Many secondary metabolites (SM) possess antibacterial, antiviral, antifungal, antiparasitic and antioxidant properties. Today these substances also have great value as cosmetics and medicines. Many are used to flavor and preserve foods. Others are used as dyestuffs and fragrances. Although the use of fungicides of synthetic origin for control of postharvest microorganisms in food plants has been limited because of the residues that remain in the products, antimicrobial agents from plants or bacteria either alone or in combination are added to food packaging materials to improve the shelf life of packaged products, control the growth of microbes and ensure that consumers obtain quality products without fungal or bacterial contamination. Some synthetic antimicrobial agents previously used for this purpose have been shown to be carcinogenic. Many compounds of current interest have been known and studied for many years, but it is only with the advent new biotechnological (genomic, proteomic and metabolomic) approaches that their biosynthesis has been understood at a level to permit their engineering in crop plants. Plant biotechnology provides new methods for elucidation of the biosynthetic pathways leading to the SMs in plants and fungi and, further, new molecular methods offer ways to understand regulation and to improve production of SM of interest. Cell and tissue cultural techniques are advantageous in comparison to extraction of natural compounds from whole plants grown in the field as culture occurs under controlled conditions. Culture methods also avoid factors such as seasonal variation and lack of a suitable climate for cultivation. However, they are often limited by inadequate understanding of factors that initiate formation and accumulation of desired compounds and by cost. Naturally occurring crop protection chemicals offer a means to meet the demand for increased food production produced by increases in global population. Regulation of traditional crop protection products in agriculture has been controversial (Seiber et al., 2014; Czaja et al., 2015; Exley et al., 2015), but use of biopesticides in modern agricultural practices based on integrated pest management (IPM) (Cantrell et al., 2012; Marrone, 2014; Singh, 2014; Seiber et al., 2014; Czaja et al., 2015; Exley et al., 2015) may help to resolve conflicts involving food production, human health and the environment. This concept has stimulated intensive research, leading development of a variety of new technologies

Table 1 Higher plants, trees, shrubs and herbs, with antibacterial activities Type of sample

Additional information

Biological evaluation

Activity

Reference

Bidens pilosa Bixa orellana (Bixaceae)

Aqueous extract Ethanol extract

Plants of traditional medicine used to treat microbial infections

Staphylococcus aureus Fr. & Fr., Streptococcus beta hemolític, Bacillus cereus, Pseudomonas aeruginosa (Schroeter) Migula, Escherichia coli

Rojas et al. (2006)

Cecropia peltata L. (Cecropiaceae) Cinchona officinalis L. (Rubiaceae) Gliricidia sepium (Jacq.) Steud. (Fabaceae) Jacaranda mimosifolia D. Don (Bignoniaceae) Justicia secunda Vahl (Onagraceae)

Ethanol extract

Activity against Bacillus cereus E. coli: 0.8 mg/mL (control with gentamycin sulfate: 0.98 g/mL) Bacillus cereus: 0.2 mg/mL (control gentamycin sulfate: 0.5 mg/ml) Active against Staphylococcus aureus

Ethanol extract

Active against Staphylococcus aureus

Ethanol extract

Active against Staphylococcus aureus

Aqueous extract

Activity against Bacillus cereus

Ethanol extract

Piper pulchrum C. DC. (Piperaceae)

Aqueous extract

Piper paniculata (Piperaceae) Spilanthes Americana Hieron. (Asteraceae) Piper lanceaefolium Kunth (Piperaceae)

Ethanol extract Ethanol extract

E. coli: 0.6 microg/mL (control with gentamycin sulfate: 0.98 g/mL) Candida albicans (C. P. Robin) Berthout: 0.5 mg/mL (control with nystatin: 0.6 mg/mL) E. coli: 0.6 microg/mL (Control with gentamycin sulfate: 0.98 g/mL) Candida albicans: 0.5 mg/mL (control with nystatin: 0.6 mg/mL) Active against Staphylococcus aureus Active against Staphylococcus aureus

Crude extract

5,7-Dihydroxyflavanone (pinocembrin) 2′,4′,6′-Trihydroxychalcone (pinocembrin chalcone) Cyclolanceaefolic acid methyl ester (prenylated benzoic acid derivative) Methanol extract

Alchornea coelophylla Pax & K. Hoffman (Euphorbiaceae) Acalypha diversifolia Jacq. Methanol extract (Euphorbiaceae) Euphorbia sp. (Euphorbiaceae) Dichloromethane extract Calea angosturana (Asteraceae) Hexane extract

Clibadium funkize (Asteraceae)

Vernonia canescens Kunth (Asteraceae) Acalypha sp. (Euphorbiaceae)

Dichloromethane extract Hexane extract Methanol extract Hexane extract Dichloromethane extract Dichloromethane extract Methanol extract Dichloromethane extract

Neisseria gonorrhoeae strains

panel of 26 NG strains comprising 12 antibioticresistant phenotypes.

Plants collected at the Natural Regional Park Ucumari (Risaralda, Colombia) altitudinal range between 2100 and 2450 m

Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 21556), Klebsiella pneumoniae (Schroeter) Trevisan (ATCC 10031), Escherichia coli (ATCC 9637), Pseudomonas aeruginosa (ATCC 27853)

Active against antibiotic susceptible Neisseria gonorrhoeae (Zopf) Trevisan, strain WHO V Inhibition of 100% of the NG panel at 64 mg/mL Inhibition of 100% of the NG panel at 128 mg/mL Inhibition of 44% of the NG panel at 128 mg/mL Inhibition of B. subtilis, P. aeruginosa, S. aureus and E. coli MIC: 4.0 mg/mL Pseudomonas aeruginosa MIC MIC: 2.0 mg/mL for Bacillus subtilis, 1.0 mg/mL for Pseudomonas aeruginosa MIC: 4.0 mg/mL for Bacillus subtilis MIC: 4.0 mg/mL for Bacillus subtilis MIC: 4.0 mg/mL for Pseudomonas aeruginosa MIC: 2.0 mg/mL for Bacillus subtilis and 0.25 for Pseudomonas aeruginosa MIC: 4.0 mg/mL for Bacillus subtilis MIC: 4.0 mg/mL for Pseudomonas aeruginosa MIC: 2.0 mg/mL for Staphylococcus aureus MIC: 4.0 mg/mL for

Ruddock et al. (2011)

Niño et al. (2012)

551

Tetrorchidium andinum Müll. Arg. (Euphorbiaceae)

Plant used by traditional healers for cutaneous infection

C.L. Cespedes et al. / Environmental Research 142 (2015) 549–562

Plant

552

Table 1 (continued ) Higher plants, trees, shrubs and herbs, with antibacterial activities Plant

Type of sample

Acalypha platyphylla Müll. Arg. (Euphorbiaceae)

Methanol extract

Alchornea coelophylla Pax & K. Hoffman (Euphorbiaceae)

Hexane extract

Additional information

Biological evaluation

Activity

Methanol extract

Hyeronima antioquiensis (Euphorbiaceae) Mabea montana Müll. Arg. (Euphorbiaceae)

Methanol extract

Ladenbergia macrocarpa (Vahl) Klotzsch (Rubiaceae)

Hexane extract

Methanol extract

Methanol extract Palicourea acetosoides VernHexane extract ham (Rubiaceae) Solanum brevifolium Dunal Methanol extract (Solanaceae) with antifungal activity (continued) Plant Type of sample Lippia alba (Mill.) N. E. Brit. Ex Britton & P. Citral oil Wilson (Verbenaceae) Citronellal oil and geraniol oil Achyrocline alata (Kunth) DC. (Asteraceae) Baccharis latifolia (Ruiz & Pav.) Pers. (Asteraceae) Mikania leiostachya Benth. (Asteraceae) Dichloromethane extract Pentacalia americana (L. f.) Cuatrec. Dichloromethane extract (Asteraceae) Calea angosturana (Asteraceae) Methanol extract Clibadium funkize (Asteraceae) Methanol extract Veronia canescens (Asteraceae) Methanol extract Acalypha sp. (Euforbiaceae) Dichloromethane extract Tetrorchidium andinum (Euphorbiaceae) Dichloromethane extract Acalypha diversifolia (Euphorbiaceae) Dichloromethane extract Hyeronima antioquiensis (Euphorbiaceae) Dichloromethane extract Mabea montana (Euphorbiaceae) Dichloromethane extract Cinchona pubescens (Rubiaceae) Dichloromethane extract Ladenbergia macrocarpa (Rubiaceae) Dichloromethane extract Solanum brevifolium (Solanaceae) Dichloromethane extract Antimicrobial activity of trees, shrubs and herbal. Plant species Family Type of sample Lepechinia caulescens (Or- Labiatae Aqueous extract tega) Epling Lepechinia caulescens (Or- Labiatae Essential oil tega) Epling

Biological evaluation Candida parapsilosis, Candida krusei, Aspergillus flavus, Aspergillus fumigatus

Activity GM-MIC: 78.7 mg/mL for Aspergillus fumigatus and 270.8 mg/mL for Candida krusei GM-MIC: 176.8 mg/mL for Aspergillus fumigatus and 49.6 mg/mL for Candida krusei Candida parapsilosis ATCC 22019, Candida krusei ATCC 6258, Aspergillus flavus GM-MIC: 78.7 mg/mL for Aspergillus fumigatus ATCC 204304, Aspergillus fumigatus ATCC 204305 (EUCAST and CLSI M38-A GM-MIC: 157.4 mg/mL for Aspergillus fumigatus standard methods, for yeast and filamentous fungi, respectively) Candida albicans (yeast), Aspergillus fumigatus, Fusarium solani? MIC: 4.0 mg/mL for Fusarium solani MIC: 4.0 mg/mL for Fusarium solani MIC: MIC: MIC: MIC: MIC: MIC: MIC: MIC: MIC: MIC: MIC:

Additional information Medicinal plant used by Purépecha Medicinal plant. borneol, camphor, transcaryophyllene and linalool

Reference Mesa-Arango et al. (2009)

Zapata et al. (2010)

Niño et al. (2012)

4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 1.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani 4.0 mg/mL for Fusarium solani

Biological evaluation Salmonella typhi, Shigella boydii. Vibrio cholerae

Activity MIC: 0.250 mg/mL

Reference Avila et al. (1993)

Vibrio cholerae

MIC: 0.003– 0.004 mg/mL

Avila et al. (2005)

C.L. Cespedes et al. / Environmental Research 142 (2015) 549–562

MIC: 1.0 mg/mL for Staphylococcus aureus, 4.0 mg/mL for Pseudomonas aeruginosa, 1.0 mg/mL for E. coli MIC: 4.0 mg/mL for Pseudomonas aeruginosa MIC: 4.0 mg/mL for Bacillus subtilis, 1.0 mg/mL for Staphylococcus aureus, Pseudomonas aeruginosa, and E. coli MIC: 4.0 mg/mL for Bacillus subtilis, 2.0 mg/mL for Staphylococcus aureus, 4.0 mg/mL for E. coli MIC: 4.0 mg/mL for Pseudomonas aeruginosa MIC: 4.0 mg/mL for Staphylococcus aureus and Pseudomonas aeruginosa, and 1.0 mg/mL for E. coli MIC: 4.0 mg/mL for Pseudomonas aeruginosa MIC: 4.0 mg/mL for Staphylococcus aureus MIC: 4.0 mg/mL for Pseudomonas aeruginosa MIC: 4.0 mg/mL for Pseudomonas aeruginosa

Methanol extract

Hyeronima macrocarpa Müll. Arg. (Euphorbiaceae)

Reference

Lepidium virginicum L.

Brassicaceae

Aqueous Extract

Medicinal plant used by Purépecha Medicinal plant used by Purépecha Medicinal plant. Verbascoside

Tanacetum parthenium (L.) Sch. Bip. Buddleja cordata Kunth

Asteraceae

Aqueous Extract

Loganiaceae

Methanol extract

Buddleja cordata

Loganiaceae

Buddleja globose Hope Cordia curassavica (Jacq.) Roem. & Schult.

Loganiaceae Boraginaceae

Methanol and aqueous extracts Methanol, aqueous Essential oil/hexane/ chloroform

Medicinal plant. linarin and linarin acetate Medicinal plant. Verbascoside Medicinal plant

Pittoccaulon spp.

Asteraceae

Dichloromethane Extracts

Medicinal and weedy plant

Gymnosperma glutinosum Less.

Asteraceae

Hexane extract

Medicinal and weedy plant. ( þ)-8S, 13S, 14R, 15-entLabdanotetrol Medicinal and weedy plant

Salmonella typhi, Shigella boydii. Vibrio cholerae

MIC: 0.250 mg/mL

Avila et al. (1993)

Salmonella typhi, Shigella boydii, Vibrio cholerae

MIC: 0.250 mg/mL

Avila et al. (1993)

Staphylococcus aureus Kinetic assay, Mode of Action

MIC: 0.4 mg/mL MBC 0.8 mg/mL MIC: 0.031–4 mg/mL

Avila et al. (1999)

Acanthamoeba castellanii, A. plyphaga S. aureus, B. subtilis, many other St. aureus; S. epidermidis; B. subtilis; S. lutra; V. cholerae; Y. enterocholitica; E. coli; A. niger; T. mentagrophytes; F. sporotrichum; F. moniliforme; R. solani S. epidermidis, Bacillus subtilis, V. cholerae, Fusarium sporotrichum, Rhizoctonia solanii, and Trychophytonmenta grophytes: Fusarium sporotrichum ATCC NRLL 3299; Aspergillus niger, Trichophyton mentagrophytes, Fusarium moniliforme Rhyzoctonia solani (wild type) Candida albicans, Klebsiella spp., Pseudomona aeruginosa.

MIC: 2.5–3.0 mg/mL

Marín-Loaiza et al. (2008)

MIC: 0.06–0.5 mg/mL.

Serrano et al. (2009), and Canales et al. (2007)

MIC: N.D.

Martinez-Vazquez et al. (1986, 1994), Cespedes et al. (2001b) Kumar et al. (2013, 2014)

Methanol

Parthenium hysterophorus L.

Asteraceae

Methanol/ dichloromethane

Medicinal and weedy lant

Larrea tridentata (DC.) Coville

Zygophyllaceae

Methanol, dichloromethane

Medicinal and weedy plant

MIC: 36.0–130.0 mg/mL Staphylococcus aureus MTCC 3160, Bacillus cereus MTCC (2.0 mg/disk) 1272, Escherichia coli MTCC 43 and three fungal strains (Candida albicans MTCC 3017, Aspergillus flavus MTCC 277, Saccharomyces cerevisiae R. solani, F. oxysporum, Pythium, others. MFC: 500–1000 mg/mL

Flourensia cernua

Asteraceae

Methanol

Medicinal and weedy plant

R. solani, F. oxysporum, Pythium, others.

Chenopodium ambrosioides L.

Chenopodiaceae Essential oil, Methanol, dichloromethane

Tagetes erecta L.

Asteraceae

Methanol, dichloromethane

T. lucida Cav.

Asteraceae

Methanol, dichloromethane

T. minuta L.

Asteraceae

Methanol

Metopium brownei

Anacardiaceae

Methanol

Medicinal, ornamental and weedy T. mentagrophytes and R. solani / E. coli and P. mirabilis plant (40%), K. pneumoniae 31.1%), Salmonella sp. (35.5%), and Shigella sp. (0%) Medicinal and weedy plant Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis Comercial and medicinal plant Phytium spp., Alternaria spp.

Capsicum spp.

Solanaceae

Methanol

Commercial and medicinal plant

Agave lechuguilla

Agavaceae

Methanol

Medicinal plant

Bacillus cereus, B. subtilis, Clostridium sporogenes, C. tetani, Wide range: 1– 100 mg/mL Streptococcus pyogenes, E. coli, Pseudomonas solanacearum, Saccharomyces cereviseae Several yeasts, molds, bacteria N.D.

Yucca carnerosana

Agavaceae

Methanol

Medicinal plant

Several bacteria and viruses

N.D.

Yucca periculosa Bidens pilosa

Agavaceae Asteraceae

Methanol Methanol

Medicinal plant Medicinal plant

Several bacteria and fungi Candida albicans, Klebsiella pneumonia, Bacillus spp., Staphyllococcus spp., Salmonella sp.

10–100 mg/mL 1–50 mg/mL

Araucaria araucana

Araucariaceae

Aqueous, methanol

Ornamental and medicinal plant

Gram þ and Gram  bacteria Fungi: F. moniliforme, A. niger, T. mentagrophytes, M.

1.0–50.0 mg/mL

Medicinal and weedy plant

Phytium spp., R. solani, Phytophthora spp., A. solani, Fusarium oxysporum, Mycobanterium tuberculosis, Plasmodium falciparum? Medicinal, ornamental and weedy Phytophthora spp., A. solani, others plant

MFC: 500–1000 mg/mL

N.D.

N.D.

12.5–250.0 mg/mL/ 0.4 mg/disk

Jasso de Rodriguez et al. (2006) and references therein Jasso de Rodriguez et al. (2006) and references therein Jasso de Rodriguez et al. (2006) and references therein Jasso de Rodriguez et al. (2006) and references therein Cespedes et al. (2006a)

100–200 mg/mL

Tereschuk et al. (1997)

N.D.

Jasso de Rodriguez et al. (2006) and references therein Jasso de Rodriguez et al. (2006) and references therein Jasso de Rodriguez et al. (2006) and references therein Jasso de Rodriguez et al. (2006) and references therein Cespedes et al. (2008) Jasso de Rodriguez et al. (2006) and references therein Cespedes et al. (2006b) 553

Parthenium argentatum A. Asteraceae Gray

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0.5–10.0 mg/mL 50.0–2.000,00 mg/mL

Rodríguez-Zaragoza et al. (1999) Pardo et al. (1993) Hernandez et al. (2007)

Cespedes et al. (2001a) and Hoeneisen et al. (1980). Martinez-Vazquez et al. (1999) 100–500 mg/mL

K. pneumoniae, P. aeruginosa, S. typhi, Sh. flexnari, S. aureus, S. epididermis, S. pneumoniae, M. luteus. Note: N.D. ¼ not determined

Methanol Malpighiaceae

Economic and medicinal plant (tree)

Methanol

Podanthus ovatifolius, P. mitiqui Byrsonima crassifolia (L.) Kunth

Asteraceae

Medicinal plant

100–500 mg/mL

Cespedes et al. (2013c) and Cespedes et al. (2014)  200 mg/mL, 60– 125 mg/mL Methanol Calceolariaceae

Ornamental and medicinal Plant

Bacteria: E. coli, E. agglomerans, B. subtilis, S.aureus. Fungi: R. solani, F. sporotrichum, F. moniliforme, A. niger, T. mentagrophytes. Various strains

Vila et al. (1999) Bhakuni et al. (1974) 2.0 mg/mL 0.5–10.0 mg/mL Medicinal plant Medicinal plant Aqueous, methanol Methanol Monimiaceae Elaeocarpaceae

Peumus boldus Molina o Aristotelia chilensis (Molina) Stuntz Calceolaria sp.

Antimicrobial activity of trees, shrubs and herbal. Plant species Family Type of sample

Table 1 (continued )

Additional information

Biological evaluation miehei, P. variotii, C. pirifera, T. versicolor, P. notatum Streptococcus pyogenes, Micrococcus sp., Candida sp, Bactericidal (many)

Reference

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Activity

554

It is noteworthy that application of biopesticides, organic methods and plant resistance to certain pests are all parts of integrated pest management (IPM) strategies for crop protection. In IPM strategies, environmentally-friendly biopesticides normally are preferred to synthetic organic pesticides. The crop protection role of biopesticides under an integrated pest management (IPM) strategy increases the benefits of these pesticides of botanical origin. The focus of this review is isolation and evaluation of bioactive compounds from Chile and Mexico. The biodiversity of Latin America has enormous potential because is an excellent source of chemical diversity for drug discovery. Despite this, a limited amount is known about the flora and the compounds that occur in plants and fungi of Mexico, Central and South America (Cespedes et al., 2006c; Carpinella et al., 2003; Diaz-Napal et al., 2010; Joray et al., 2013). Latin America is one of the world’s most biodiverse regions harboring almost 20% of the total flora. The Andes Mountains stretch from Colombia to Tierra del Fuego in South America in a north–south corridor. The orogeny of this mountain chain is considered to have been one of the most important events for the development of current botanical diversity in South America. Similar mountain chains and associated biodiverse regions are found in Mexico and Central America. Floristic exchange has occurred in both directions since Early Miocene times (Luebert and Weigend, 2014). Thus, these regions are also among the richest for production of novel SM (Svetaz et al., 2013; Aqueveque et al., 2010a,b). These natural resources display considerable geographic and habitat diversity. A large number of the plant natural resources are herbaceous plants, shrubs, and trees fungi that along with fungi inhabit temperate areas or deserts with extended periods of drought (Luebert and Weigend 2014). The search for secondary metabolites in plants and fungi associated with Andean and Mexican forests has revealed a previously unsuspected reservoir of new and potentially useful molecules. Our research group has not only focused on endemic taxa but also on cosmopolitan species that have colonized our forests. Many cosmopolitan species that colonize Andean environments are subjected to new growing conditions that can cause modifications in their normal biosynthetic pathways generating new compounds, thereby allowing adaptation to new living conditions. Abies spp., Hypericum perforatum L, a Cammelina sp., Eschscholtzia californica Cham., Eucalyptus spp., Pinus spp., a Vaccinium sp., Serpula himantioides (Fr.) Karst, Gymnopilus spectabilis (Fr.) Smith, and Chondrostereum purpureum (Pers. ex Fr.) Pouzan, are widely distributed in Chilean native forests. They appear to have generated both new and active compounds, as well as known compounds confirming the importance of exhaustive collections and screening programs even for well-known introduced plant from all available habitats. Current interest in the application of plant and fungal SM for pest management highlights the importance of the search for new sources of biologically active natural products with biodegradability, low mammalian toxicity and environmentally-friendly qualities (Cespedes et al., 2014). For more effective and environmentally-friendly pest control, we propose use of organic molecules from botanical and fungal origin (Muñoz et al., 2013a,b; Cespedes et al., 2008; 2014).

2. The most promising botanical families with biocidal potential Phytochemicals from a number of families of plants and fungi from the southern Andes and from Mexico have now been evaluated (Cespedes et al., 2006c). The most important of these are

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from the Agavaceae, Anacardiaceae, Araucariaceae, Asteraceae, Buddlejaceae, Calceolariaceae, Celastraceae, Elaeocarpaceae, Lauraceae, Monimiaceae, Rhamnaceae, Scrophulariaceae, and Winteraceae (Table 1). A series of compounds from fungal families also is reported. The information has been organized in sections that include selected botanical families and relevant fungi that may serve as sources of new fine chemicals with biocidal properties that may prove valuable for the fight in the pest control and phytopathogens (Table 1). 2.1. Higher plants 2.1.1. Agavaceae Yucca periculosa F. Baker, known commonly as “palmitos” or “izote” is a tree-like monocotyledonous plant, endemic to Mexico, that grows in the semi-arid regions of Tehuacan-Cuicatlan Valley, Puebla–Oaxaca States. In the wild, these plants survive under different environmental stress conditions (Casas et al., 2001), with a lifespan of up to 100 years. Our field observations indicate that this species has strong resistance to insect attack (Torres et al., 2003; Cespedes et al., 2006c). Additionally, triterpenes with antibacterial activity have been isolated from Y. carnerosana (Trel.) McKelvey and Y. recurvifolia Salisb. (Jasso de Rodriguez et al., 2006). In a similar manner, a saponin from “lechuguilla” Agave lechuguilla Torrey with very interesting antibacterial activity also has been isolated (Jasso de Rodriguez et al., 2006). 2.1.2. Anacardiaceae Metopium brownei (Jacq.) Urb., a tree 12–25 m tall, produces eriodictyol, which has antifeedant and antifungal activity (Jasso de Rodriguez et al., 2006). This species also contains anacardic acid which is present in “mango” Mangifera indica L. (Kubo et al., 2011). The fruits of Schinus molle L., are widely used and commonly known as a spice called “pink pepper” or “American pepper”. This plant is a tree native to subtropical lands of South America, but widely cultivated and adventive in much of the tropical world. Substances from the seeds of this species contain compounds with antioxidant, antimicrobial and toxicological properties (Martins et al., 2014). 2.1.3. Asteraceae Strong resistance against oxidative stress and pest attack in nature has been observed in many American members of the Asteraceae. A large number possess excellent ethnomedicinal data. Based on chemical literature, several species of this family such as Bidens pilosa L., Baccharis spp., Cosmos spp., Flourensia cernua DC., Gutierrezia microcephala (DC.) A. Gray, G. gayana (J. Rémy) Reiche, Gutierrezia spp., Happlopappus spp., Helianthus spp., Heterothalamus spp., Podanthus ovatifolius Lag., P. mitiqui Llindl., Parastrephia quadrangularis (Meyen) Cabrera, Roldana barba-johannis (DC.) H. Rob. & Brettell, Tagetes lucida Cav., Tagetes spp., Vernonia spp., and Vernonanthura tweediana (Baker) H. Rob., have been evaluated for their antioxidant, antibacterial, antifungal and IGR activities (Table 3). Several flavonoids, coumarins, sesquiterpene lactones and phenolics have been isolated from various members of the Asteraceae (Cespedes et al., 2006c). For example, a phytochemical study of Podanthus ovatifolius led to the isolation of ovatifolin (Cespedes et al., 2001a; Hoeneisen et al., 1980). Two species that grow in the rain forest of Pacific slopes of the Araucanian Region of southern Chile, P. mitiqui and P. ovatifolius, are small shrubs with very good antibacterial activity (Bhakuni et al., 1974). Tagetes lucida, “pericón”, is a medicinal plant used from preColumbian times by Aztecs and other Mesoamericans. The leaves and inflorescences are used for stomachache and as an anti-

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inflammatory for treatment of diverse ailments. From a dichloromethane extract, we isolated several coumarins: scopoletin (6-methoxy-7-hydroxycoumarin), esculetin (6,7-dihydroxycoumarin), 7-methoxy-6-hydroxycoumarin, scoparone (6,7-dimethoxy-coumarin) and their derivatives 6,7-diacetoxycoumarin, and 6-methoxy-7-acetoxycoumarin (Cespedes et al., 2006a,b,c). We also reported the antibacterial and antifungal activity of extracts and compounds from T. lucida. In this case, the dihydroxylated coumarins are active against Gram-positive bacteria and the dimethoxylated coumarins are active against several human and phytopathogenic fungi (Cespedes et al., 2006a). From the large genus Baccharis with approximately 350 species, only a few are important medicinal plants. However, their uses seem to be rather diverse and more than 50 species have been investigated chemically. We have studied B. conferta Kunth, B. linearis Poepp. ex Baker, B. magellanica Pers., B. salicifolia (Ruiz & Pav.) Pers. and B. umbelliformis DC. (Cespedes et al., 2001a,b,c). These species possess outstannding phytotoxic, herbicidal and antifeedant and biological activity. 2.1.4. Araucariaceae Because of their strong resistance against insect attack, as a part of our search for natural products with possible insecticidal activity, we studied several gymnospermous trees of the rain forest of southern Chile. Among them were the conifers Araucaria araucana (Molina) K. Koch and A. angustifolia (Bertol.) Kuntze, endemic to the rain forest of southern Chile and northeastern Argentina. These species are unique and have great commercial, agroforestry, ethnobotanical, taxonomic, and ecological value derived from their long biogeographical isolation and are strongly resistant to pest attack. These facts offer a good opportunity for the search of secondary metabolites, in particular, those that play a defensive role against pathological and phytophagous pests. Five lignans (secoisolariciresinol, lariciresinol, pinoresinol, eudesmin, and methylpinoresinol) were isolated from MeOH extracts of bark and wood of A. araucana and their structures determined with spectroscopic methods. In addition to antifeedant, insecticidal and insect growth regulation (IGR) activities against Spodoptera. frugiperda (J.E. Smith) (fall army worm, FAW), the antibacterial activity of these compounds was determined against Gram-positive and Gram negative bacteria and the antifungal activity against Fusarium moniliforme Shel., Aspergillus niger van Tiegham, Trichophyton mentagrophites (C. P. Robin.) Sabour, Mucor miehei Cooney & Emersonb, Paecilomyces variotii Bainier, Ceratocystis pilifera (Fr.) C. Moreau, Trametes versicolor (L.) Lloyd and Penicillium notatum Westling. These lignans exhibited both antifungal and antibacterial activity (Cespedes et al., 2006b) and served as antifeedants for FAW, at dosages between 1.0 and 50.0 ppm. 2.1.5. Calceolariaceae Calceolaria L. (Calceolariaceae: formerly Scrophulariaceae) is a widespread and common genus in the Andean region, distributed from Patagonia to Colombia, and then northward as far as northwestern Mexico. The last revision of this genus recognized more than 180 species with three subgenera, restricted to the Americas (Molau, 1988, 2003): Calceolaria (19 sections), Cheiloncos (two sections), and Rosula (three sections) (Anderson, 2006). Ehrhart (2000, 2005) revised the Chilean representatives of the genus and recognized 50 species, among them the Calceolaria integrifolia L. s. l. complex with nine species: Calceolaria andina Benth., Calceolaria angustifolia (Lindl.) Sweet, Calceolaria auriculata Phil., Calceolaria georgiana Phil., C. integrifolia s. str., Calceolaria rubiginosa C. Ehrh., Calceolaria talcana J. Grau & C. Ehrh., Calceolaria verbascifolia Phil., and Calceolaria viscosissima (Hook.) Lindl. (Ehrhart, 2005). Many of these species are commonly known as “zapatito de doncella” or “capachito de hoja larga”. Generally they are strong, erect shrubs

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that grow from 50 to 150 cm, although depending on locality, they may only reach a shorter height with fragile ascending branches. Despite the relatively few studies of biological activity of the secondary metabolites isolated from Calceolaria species, these species have been shown to be antifeedant, tyrosinase/acetylcholinesterase inhibitors, antibacterial, antifungal, antioxidant, and trypanocidal (Cespedes et al. 2015a,b). Only 15% of existing species of Calceolaria in Chile have been studied chemically, but they have been shown to contain flavonoids, glucophenylpropanoids, and diterpenes. Recently, we published an updated review of the chemistry of Calceolaria (Cespedes et al., 2013c). Systematic study of the chemical constituents of Calceolaria led to the discovery a number of new molecules; a total of 117 compounds have been reported to date (Cespedes et al., 2013c). Bioactivity in both Gram-positive and Gram-negative bacteria were examinated in antibacterial bioassays. At different levels; flavonoids, ferulic acid and diterpenes were active against almost all Gram-positive and Gram-negative bacteria assayed at various dosages. Diverse mixtures M1 (quercetin þferulic acid), M2 (kaempferolþferulic acid), M3 (isorhamnetinþ ferulicacid), M4 (myricetin þferulic acid) and M5 (dunnione þgallic acid) were assayed against enterobacteria and fungi, respectively. M3 showed an inhibitory effect against E. coli (Migula) Castellani & Cham., Enterobacter agglomerans Ewing & Fife, a Salmonella sp., Bacillus subtilis Cohen, Staphylococcus aureus and Staphylococcus lutra Foster et al.; this effect was noticeably greater in E. coli, E. agglomerans and a Salmonella sp. than for the other bacteria assayed. These results showed that mixture M3 and its components had significant inhibitory activity. Mixtures M3, M5 and diterpenes were also assayed against the fungi Rhizoctonia solani Kühn, Fusarium sporotrichum, F. moniliforme J. Sheld., and A. niger. The activity level shown by dunnione and M5 against these fungi was relatively high as compared with the positive control (ketoconazole). M5 was the most active of all samples assayed in a manner similar to that reported by Khambay et al., 2003. Mixture M3 completely inhibited the mycelial growth of these fungi above 4000 mg/disk. The growth of A. niger, F. monoliforme, F. sporotrichum, and R. solani was completely inhibited by M5 in a range of 1500–5000 mg/disk. In view of the strong activity of M3 against bacteria, and M5 against fungi, these samples and several compounds were assayed against different fungal and bacterial strains and their minimum inhibitory concentration (MIC), minimum bactericide concentration (MBC), FC50, and MFC values were obtained (Cespedes et al., 2014). The values for these compounds are close to those of the positive control; which renders them quite important due to possible use of these substances as biopesticides. Many of these compounds have also been previously reported from other members of Calceolaria (Cespedes et al., 2013c). Interestingly, the total MeOH extract of C. integrifolia  C. talcana and of C. integrifolia have the largest percentage of phenolic compounds of any of these plants (Cespedes et al., 2013a,b,c). The pronounced inhibition of bacterial and fungal growth could explain the strong resistance to the attack of pathogenic organisms by this hybrid species (Cespedes et al., 2014). 2.1.6. Celastraceae The family Celastraceae is cosmopolitan, but occurs in both tropical and subtropical regions from South America. The family consists of approximately 88 genera and 1300 species; the great majority of the genera are tropical. These plants are small trees, bushes, or lianas, often with resinous stems and leaves. They have been valued since antiquity because of their useful medicinal properties. Anti-tumor, anti-leukemic, antibacterial, insecticidal and insect repellent activities have been attributed to crude plant extracts of the Celastraceae used in traditional medicine and agriculture. Plant extracts of the Celastraceae have been used

throughout South America as insect repellents and insecticides in traditional agriculture. Many of these interesting properties may be attributed to a large family of highly oxygenated sesquiterpenoids based on a tricyclic dihydroagarofuran skeleton (Alarcon et al., 2011; Cespedes et al., 2001c; Spivey et al., 2002). 2.1.7. Rhamnaceae The Rhamnaceae is a cosmopolitan family of flowering plants, consisting of  50 genera and  900 species, mostly trees, shrubs, and some vines, and one herb, which is more common in the subtropical and tropical regions. It is commonly called the Buckthorn family. The earliest fossil evidence of Rhamnaceae is from the Eocene (Richardson et al., 2000). These plants are characterized by flowers with petal-opposed stamens (obhaplostemony) and a tendency toward xeromorphism. Obhaplostemony is a relatively rare feature in angiosperms, and this has resulted in Rhamnaceae being associated with other families such as Vitaceae and Cornaceae exhibiting this arrangement (Richardson et al., 2000). The xeromorphic adaptations exhibited by some members of the family include reduced or absent leaves, crowding of leaves, shortening of branch axes, presence of thorns or spines, and low, shrubby habit. There are few plants of economic value in Rhamnaceae, the most notable being the jujube (Ziziphus jujuba A. Mill.), a fruit tree, and ornamental shrubs Ceanothus, Colletia and Colubrina spp. (Alarcon and Cespedes, 2015; Dominguez-Carmona et al., 2011; Roitman and Jurd, 1978; Richardson et al. 2000). Chilean Rhamnaceae are spiny shrubs found in the central zone of Chile. In Chile, there are 30 species distributed in 7 genera. Following work done in the genus Colletia, the number of species has been reduced to 18 in the same 7 genera. Important Chilean genera are: Colletia (6), Condalia (1), Discaria (5), Retanilla (2), Rhamnus (1), Talguenea (1), and Trevoa (1) (Alarcon et al., 2011; Alarcon and Cespedes 2015). There are limited studies of the biological activity of compounds isolated from Chilean Rhamnaceae. Alkaloids and pentacyclic triterpenes (PTs), as mentioned above, are characteristic chemicals found in this family. In particular, PTs possess several types of biological activity including anti-HIV, antitumor, antidiabetic, anti-inflammatory, antibacterial, antiviral, antiparasitic, hepatoprotective, wound healing, antioxidant, antipruritic, antiangiogenic, antiallergic and immunomodulatory activities (Zhang et al. 2011). Benzylisoquinoline alkaloids constitute a group of natural products of diverse structure that are widely present in many plants including Rhamnaceae, but also have been reported from mammalian species. About 2500 1-benzylisoquinoline alkaloids have been identified and shown to have a wide range of biological activities including anticancer, antimalarial, anti-HIV, antiplatelet and vaso-relaxant. Several natural and synthetic benzylisoquinoline derivatives have also displayed affinities for dopamine and serotonin receptors,which are important neurotransmitters in the central nervous system (CNS) (Hawkins and Smolke, 2008). 2.1.8. Biologically active compounds from other families Among Andean and montaine species of Mexico, many have agrochemical, biocidal and ethnomedical uses. Among them are: Acantholippia punensis Botta (rica-rica, Verbenaceae), Artemisia copa Phil. (copa-copa, Asteraceae), an Artemisia sp., Azorella compacta Phil. (yareta, Apiaceae), Bixa orellana L. (achiote, Bixaceae), Capsicum spp. (chiles, Solanaceae), Chenopodium sp. (epazote, paico, Amaranthaceae), Ephedra andina (Poepp.) Stapf (pingopingo, Ephedraceae), Haplopappus rigidus (Rydb.) Blank. (Asteraceae), Haplopappus spp. (baylahuen), Helenium atacamense Cabrera, Helenium sp. (manzanilla), Lampaya medicinalis Phil. (lampaya, Apiaceae), Mulinum crassifolium Phil. (chuquican, Apiaceae),

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Table 2 Distribution of antimicrobial activities found in taxonomic groups investigated. Order

No. of species

Agaricales 45 Boletales 14 Cortinariales 13 Ganodermatales 5 Hymenochaetales 3 Polyporales 31 Russulales 4 Schizophyllales 6 Sterales 23 Thelephorales 2 Tremellales 3 Total 149

No. of active strains

No. of strains with No. of strains with antifungal antibacterial activity activity

27 10 8 0 3 18 1 2 16 0 2 87 (58.3%)

20 10 7 0 0 15 1 1 12 0 1 67 (44.9%)

21 6 7 0 3 15 0 1 15 0 2 70 (46.9%)

Aqueveque et al. (2010b).

Parastrephia quadrangularis (Meyen) Cabrera (tola, Asteraceae), Senecio graveolens Wedd. (Asteraceae), S. orophyton (chachacoma, Asteraceae), Theobroma cacao L. (cacao, Malvaceae, formerly Sterculiaceae), Piper nigrum L. (black pepper, Piperceae), a Piper sp. (pimienta), and several members of Cedrela, Guarea, and Trichillia (Meliaceae) that grow between Colombia and Mexico. These species have many biocidal activities and need more in depth studies. Finally it is important to mention investigation of the effect of essential oils from many aromatic plants, and their applications as biocides in pest control (Vila et al., 1999; Hernandez et al., 2007; Mesa-Arango et al., 2009; Zapata et al., 2010; Vergis et al., 2015; Seow et al., 2014; Martins et al., 2014). 2.2. Fungi For many years the continuing search for secondary metabolites from filamentous fungi has led to chemical innovation and the discovery of active molecules. Many of these are now widely used as antibiotics. Symbiotes, saprophytes, endophytes, and other associations of organisms often contain unknown compounds and are a little explored source of bioactive fine chemicals (Table 2). Secondary metabolites such as p-anisaldehyde and 3-chloro-panisaldehyde isolated from the basidiomycete Hypholoma capnoides (Fr.) P. Kumm.; p-anisaldehyde, 3-chloro-p-anisaldehyde, 3,5-dichloro-4-methoxybenzyl alcohol and naematolon from H. fasciculare (Huds.) Quél Champ.; and 3,5-dichloro-4-methoxybenzyl alcohol and marasmal from H. sublateritium (Fr.) Quél. (Aqueveque et al., 2010a,b), and several triterpenes and statins from a Pleurotus sp. (Alarcon et al., 2003; Alarcon and Aguila, 2006; Nieto and Chegwin, 2008; Chegwin and Nieto, 2014), showed the most potent biological activity, inhibiting a number of bacteria and fungi that were examined. Naematolon and marasmal showed medium levels of activity. Polyacetylenes isolated from G. spectabilis (Fr.) Smith exhibited powerful antifungal activity and mid-level antibacterial activity (Aqueveque et al., 2006). Fabian et al. (1998) isolated radulone A and radulone B from Radulomyces confluens (Fr.) M. P. Christ. Radulone A produced powerful inhibition of human platelet aggregation. In our studies, the same compound from C. purpureum had significant antimicrobial activity (Table 3). Gehrt et al. (1998) isolated nitidon, a new and powerful cytotoxic metabolite from Junghuhnia nitida (Pers.) Ryvarden, a cosmopolitan fungus collected in the native forests of the Nahuelbuta National Park, Chile. An alkaloid, 3-formyl-2,3-dihydroindol, was isolated from Daedalea quercina (L.) Pers. (Table 3). This alkaloid is known to inhibit the fungi Mucor miehei Cooney & R. Emers. [ ¼ Rhizomucor miehei (Cooney & R. Emers.) Schipper]

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and Nematospora coryli Peglion, although it showed no antibacterial activity. Tephrocybe spp. produced illudin C, a powerful anticancer diterpene isolated previously from a species of the genus Psathyrella (Lorenzen and Anke, 1998). These metabolites exhibited powerful activity, inhibiting both bacteria and fungi (Aqueveque et al., 2010a,b) (Table 3). Four new bioactive metabolites were identified from the fungus S. himantioides: himanimides A, B, C, and D. This group of compounds showed impressive biological activity, inhibiting the growth of bacteria and fungi (Aqueveque et al., 2002). Another new metabolite, favolon B, was isolated from a Mycena sp. This triterpene showed powerful and selective inhibition only against phytopathogenic fungi including Aspergillus ochraceus K. Wilh., Alternaria porri (Ellis) Ciferri, Botrytis cinerea Pers., Penicillium notatum, Paecilomyces variotii and Ustilago nuda (Jens.) Kellem (Aqueveque et al., 2005). In contrast, Ganoderma spp., distributed widely in the Americas, are a rich source of bioactive metabolites such as ganoderic acid, ganoderol, ganodermatriol, as well as other interesting compounds (Paterson, 2006). A study of macromycetes from the Chilean Andes demonstrated the presence of many bioactive metabolites of distinct chemical structures (Reinoso et al., 2013; Aqueveque et al., 2015). Additionally, the effect of UVB radiation on growth and antibacterial activity has been examined (Becerra et al., 2014). The level of bioactivity and diversity of chemical structures showed a great difference between plants and fungi. The number of bioactive compounds isolated from particular fungi is greater than those obtained from plants (see Tables 1–3).

3. Conclusions The results of botanical, mycological, and phytochemical work will provide useful guides for selection of the most promising botanical and fungal resources, some of which may lead to commercialization of botanical and mycological biopesticides in the future. It is important to reduce the use of synthetic pesticides, not least through the promotion of sustainable alternative solutions such as use of biopesticides in organic farming and as a part of IPM strategies (Rosner and Markowitz, 2013; Rhodes et al., 2013). In this regard, substances of botanical and fungal origin from Andean and Mexico regions of biodiversity emerge as strong alternatives to the use of synthetic pesticides. It is important to note that many of the extracts, mixtures and compounds obtained from the species described in this review possess exceptional activity; fungi are one of the most promising sources of bioactive molecules. Andean basidiomycetes are a great source of scientifically new compounds that are interesting and potentially useful. These fungi should be collected, described, studied chemically and the compounds examined for biological activity before human intervention in the forests causes their disappearance. At present, the negative effects of toxic and persistent pesticides on the environment and biodiversity, as well has human health, indicate that environmentally-friendly biopesticides should be preferred. Nonetheless, the risks and benefits of new biopesticides from botanical and fungal origin must be assessed on a sound scientific basis. It is important to bring about a significant reduction in the use of persistent pesticides, not least through the promotion of sustainable alternative solutions such as organic farming and IPM. New production of the plant and fungal sources of active compounds will have to be developed by agrochemical industries who will assess the biopesticidal market in relation to crop production and sale of organic foods. Much research is still needed to achieve these goals.

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Table 3 Compounds isolated from liquid mycelial cultures of fungi (taken from Aqueveque et al., 2010a, with modifications). Name, formula, molecular weight

Structure

Organism

Antibacterial activity

Antifungal activity

Radulone B, C25H24O2, 236.350

Chondrostereum purpureum 05-148. Radulomyces confluens

Ac, Bb, Bs, Ci, Es, Ml

Mn, Nc, Sc, Pv, Aqueveque Pn et al., (2010a) and Fabian et al. (1998)

Radulone A, C25H23O3, 251.35

Chondrostereum purpureum 05-148. Radulomyces confluens

Ac, Bb, Bs, Ci, Es, Ml

Mn, Nc, Sc, Pv, Aqueveque Pn et al. (2010a) and Fabian et al. (1998)

3-Formyl-2,3-dihydroindol, C9H9NO, 147.174

Daedalea quercina 95106

No activity

Mn, Nc

Aqueveque et al., 2010a

4,6-Diyn-3-heptanol, C7H8O, 108.138

Gymnopilus spectabilis 95105

Bb, Sa, Sp

Aqueveque et al. (2010a)

7-Chloro-4,6-diyn-3-heptanol, C7H7ClO, 142.583

Gymnopilus spectabilis 95105

Bb, Sa, Sp

p-Anisaldehyde, C9H1002, 150.174

Hypholoma capnoides 95123 Hypholoma fasciculare 04-27, 0478, 04-84, 04-146

No activity

An, Bc, Fo, Mm, Nc, Pv, Pn An, Bc, Fc, Fo, Mm, Nc, Pn, Pv No activity

3-Chloro-p-anisaldehyde, C9H9ClO2, 184.619

Hypholoma capnoides 95123 Hypholoma fasciculare 04-27, 0478, 04-84, 04-146, 95091

No activity

No activity

Aqueveque et al. (2010a)

3,5-Dichloro-4-methoxybenzyl, C8H8Cl202, 207.053

Bb, Bs, Sa Hypholoma fasciculare 04-27, 04-78, 04-84,04-146, 95091 Hypholoma sublateritium 96187

An, Bc, Fo, Mm, Nc, Pv, Pn

Aqueveque et al. (2010a)

Naematolon, C18H24O4, 304.381

Hypholoma fasciculare 04-27, 04-78, 04-84

Fo, Mm, Nc

Aqueveque et al. (2010a)

Sa

Reference

Aqueveque et al. (2010a) Aqueveque et al. (2010a)

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Table 3 (continued ) Name, formula, molecular weight

Structure

Organism

Antibacterial activity

Antifungal activity

Reference

Marasmal, C15H22O4, 266.333

Hypholoma sublateritium 96187

Bb, Bs, Sa

Fo, Mm, Nc

Aqueveque et al. (2010a)

Illudin C, C15H20O2, 232.318

Tephrocybe spp. 95090

Bb, Bs, Ml

Mm, Nc, Pv, Pi Aqueveque et al. (2010a)

Nitidon

Junghunia nitida Strain 95055

S. sp., Bs,

Rg, Sc,Pn,Fo, Mm, Nc

Gehrt et al. (1998)

MS-3 (3-Hydroxy-4, 5-bis (hydroxymethyl)-2-(3‴methyl-2‴-butenyl)-phenyl 2′, 4′-dihydroxy-6′-methyl benzoate), C21H24O7, 388,411

Stereum rameale

Bacillus cereus, B. subtilis, Staphylococcus aureus

No Activity

Aqueveque et al. (2015)

Himanimide A, C22H22O3N, 348.160

Serpula himantioides 95099

No activity

Pi

Aqueveque et al. (2010a,b)

Himanimide B, C22H24O5N, 382.165

Serpula himantioides 95099

Bb

Pi

Aqueveque et al. (2010a)

Himanimide C, C22H22O4N, 364.154

Serpula himantioides 95099

Ac, Bb, Bs, Bl, Mp, St

Ag, Ap, Ao,Cc, Aqueveque Cl, Ff, Mm, Nf, et al. (2010a) Pi, Sc, Zm

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Table 3 (continued ) Name, formula, molecular weight

Structure

Organism

Antibacterial activity

Antifungal activity

Reference

Himanimide D, C22H24O4N, 366.170

Serpula himantioides 95099

No activity

Mm, Sc

Aqueveque et al. (2010a)

Favolon B, C33H51O8, 575.358

Mycena chlorinella (J. No activity E. Lange) Singer, 96180

Ap, Ao, Bc, Mm, Pv, Pn, Un

Aqueveque et al. (2010a)

Vibralactone, C12H16O3, 208,253

Stereum rameale (Berk.) Massee

Bacillus cereus, B. subtilis, Staphylococcus aureus

No activity

Aqueveque et al. (2015)

Vibralactone B, C12H16O4, 224,253

Stereum rameale

Bacillus cereus, B. subtilis, Staphylococcus aureus

No activity

Aqueveque et al. (2015)

Abbreviations used for Bacteria: Ac: Arthrobacter citreus Sacks; Bb: Bacillus brevis Migula; Bl: Bacillus licheniformis (Weigmann) Chester; Bs: Bacillus subtilis (Ehrenberg) Cohn; Ci: Corynebacterium insidiosum (McCulloch) Jensen; Ec: Escherichia coli (Migula) Castellani and Chalmers K12; Ml: Micrococcus luteus (Schroeter) Cohn emend. Wieser et al.; Mp: Mycobacterium phlei Lehmann and Neumann; Sa: Staphylococcus aureus Rosenbach; Sp: Streptococcus pyogenes Rosenbach; St: Salmonella typhimurium (Loeffler) Castellani and Chalmers TA-98. Yeasts: Nf: Nadsonia fulvescens (Nadson & Konok.) Syd.; Nc: Nematospora coryli Peglion; Sc: Saccharomyces cerevisiae Meyen ex E. C. Hansen s1. Filamentous fungi: Ag: Absidia glauca Hagem; An: Aspergillus niger Tiegh.; Ao: Aspergillus ochraceus G. Wilh.; Ap: Alternaria porri (Ellis) Cif.; Bc: Botrytis cinerea Pers.; Cc: Cladosporium cladosporioides (Fresen.) G. A. de Vries; Cl: Curvularia lunata (Wakker) Boedijn ( ¼ Cochliobolus lunatus R. R. Nelson & Haasis); Fc: Fusarium ciliatum Link; Ff: Fusarium fujikuroi Nirenberg; Fo: Fusarium oxysporum Schltdl.; Mm: Mucor miehei Cooney & R. Emers. [ ¼ Rhizomucor miehei (Cooney & R. Emers.) Schipper]; Pi: Penicillium islandicum Sopp; Pn: Penicillium notatum Westling (¼ P. chrysogenum Thom.); Pv: Paecilomyces variotii Bainier; Un: Ustilago nuda (C.N. Jensen) Rostr. ( ¼U. nuda f.sp. hordei Schaffnit); Zm: Zygorhynchus moelleri Vuill.

Acknowledgments The authors are indebted to M.Sc. Evelyn Muñoz (Phytochemical Ecology Lab, Basic Sciences Dept., Faculty of Sciences, University of Bio Bio, Chillan, Chile) for technical assistance with the antioxidant assay and for the help in performing many insect feeding assays. To Prof. Ana Ma. García-Bores (Laboratorio de Fitoquímica, Unidad UBIPRO, FES-Iztacala, UNAM, México DF, México) for proteinase assays and performing antimicrobial assay in part. To Prof. David S. Seigler, Ph.D. (Emeritus Professor, Department of Plant Biology, and Curator, Herbarium of University of Illinois at Urbana-Champaign) for identification of the plant samples. This paper is based on work financially supported in part by grants from the Comision Nacional de Investigacion Cientifica y

Tecnologica de Chile (CONICYT-Chile), through FONDECYT Program Grant nos. 1101003 and 1130242 to C.L.C. who is very grateful. I.K. and C.L.C. are grateful to CONICYT–UC–CLAS BerkeleyChile Seed Funds Program for grant. J.A. is thankful for the support provided by Fondecyt-Chile (Project no. 1130436). P.A. wishes to express his thanks to International Foundation for Science (IFSGrant no. F/3972-1) and Fondecyt No. 11100331. C.B. to Fondecyt Grant no. 1150764.

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