Leslie Gunatilaka

Professor, Natural Resources and the Environment

Director, Natural Products Center

Professor, Pharmacology and Toxicology

Professor, Cancer Biology - GIDP

Professor, Arid Lands Resources Sciences - GIDP

Professor, BIO5 Institute

Primary Department

School of Natural Resources and the Environment

Department Affiliations

School of Natural Resources and the Environment

BIO5 Institute

Contact

(520) 621-9932

leslieg@ag.arizona.edu

Work Summary

Discovery of natural products from plants and their associated microorganisms as potential drugs to treat cancer. Application of medicinal chemistry approach for structure-activity relationship studies and to obtain compounds for preclinical evaluation. Development of alternative agricultural systems for sustainable utilization of natural resources.

Research Interest

Despite many therapeutic successes, cancer remains a major cause of mortality in the US. Natural products (NPs) represent the best source and inspiration for the discovery of drugs and molecular targets. Our aim is to discover effective and non-toxic NP-based anticancer drugs. Working with NCI we have recently discovered a class of plant-derived NPs useful in cancer immunotherapy. The main focus of our current research is to utilize medicinal chemistry approach to obtain their analogues for preclinical evaluation. Leslie Gunatilaka is Professor at the School of Natural Resources and the Environment and Director of the Natural Products Center. He is also Adjunct Professor of Department of Nutritional Sciences, and a member of the Arizona Cancer Center. He is a member of several professional societies, editorial boards, and pharmaceutical company advisory groups. He is a Fellow of the Academy of Sciences for the Developing World (TWAS), Italy, and the National Academy of Sciences, Sri Lanka. Dr. Gunatilaka has over 200 peer-reviewed publications and book chapters and over 150 communications in natural product science to his credit. He is the recipient of the Sri Lankan Presidents’ gold medal for “creating a center of excellence in natural products research at the University of Peradeniya, Sri Lanka” (1987), CaPCURE award for “dedication to ending prostate cancer as a risk for all men and their families” (2000), Research Faculty of the Year Award of the UA College of Agriculture and Life Sciences (2003), the UA Asian American Faculty, Staff and Alumni Association Outstanding Faculty Award (2005), and the UA Leading Edge Researcher Award for Innovative Research (2012). He has delivered over 100 invited lectures worldwide and was the Chief Guest and Plenary Lecturer at the International Herbal Medicine Conference held in Sri Lanka (2005), and the Keynote Speaker and the Guest of Honor at Chemtech-2007, an International Conference organized by the Institute of Chemistry, Ceylon. His current research interests include discovery, identification of protein targets, and structure-activity relationship (SAR) studies of natural product-based drugs to treat cancer, neurodegenerative, and other diseases from plants, and plant- and lichen-associated microorganisms, maximization of chemistry diversity and production of microbial and plant secondary metabolites, and scientific investigation of medicinal plants and herbal supplements. Keywords: Natural Product-Based Drug Discovery, Medicinal Chemistry, Cancer Immunotherapeutic Agents

Publications

Phomapyrrolidones A-C, antitubercular alkaloids from the endophytic fungus Phoma sp. NRRL 46751

Wijeratne, E. M., He, H., Franzblau, S. G., Hoffman, A. M., & Gunatilaka, A. A. (2013). Phomapyrrolidones A-C, antitubercular alkaloids from the endophytic fungus Phoma sp. NRRL 46751. Journal of natural products, 76(10), 1860-1865.

Three new alkaloids, phomapyrrolidones A-C (1-3), bearing a cyclopenta[b]fluorene ring system were isolated from the mycelium extract of the endophytic fungal strain Phoma sp. NRRL 46751, inhabiting Saurauia scaberrinae. Methylation of 1 afforded its N-methyl derivative 4. The planar structures and relative configurations of 1-4 were elucidated by extensive spectroscopic analysis. Phomapyrrolidones B (2) and C (3) exhibited weak antitubercular activity at subcytotoxic concentrations.

Secoemestrin D, a cytotoxic epitetrathiodioxopiperizine, and emericellenes a-e, five sesterterpenoids from emericella sp. AST0036, a fungal endophyte of astragalus lentiginosus 1

Xu, Y., Espinosa-Artiles, P., Liu, M. X., Arnold, A. E., & A., A. (2013). Secoemestrin D, a cytotoxic epitetrathiodioxopiperizine, and emericellenes a-e, five sesterterpenoids from emericella sp. AST0036, a fungal endophyte of astragalus lentiginosus 1. Journal of Natural Products, 76(12), 2330-2336.

PMID: 24251417;Abstract:

A new epitetrathiodioxopiperizine, secoemestrin D (1), and five sesterterpenoids bearing a new carbon skeleton, emericellenes A-E (2-6), together with previously known fungal metabolites, sterigmatocystin (7), arugosin C (8), and epiisoshamixanthone (9), were obtained from the endophytic fungal strain Emericella sp. AST0036 isolated from a healthy leaf tissue of Astragalus lentiginosus. The planar structures and relative configurations of the new metabolites 1-6 were elucidated using MS and 1D and 2D NMR spectroscopic data. All compounds were evaluated for their potential anticancer activity using a panel of six tumor cell lines and normal human fibroblast cells. Only metabolites 1 and 7 showed cytotoxic activity. More importantly, secoemestrin D (1) exhibited significant cytotoxicity with IC50 values ranging from 0.06 to 0.24 μM and moderate selectivity to human glioma (SF-268) and metastatic breast adenocarcinoma (MDA-MB-231) cell lines. © 2013 The American Chemical Society and American Society of Pharmacognosy.

Zinagrandinolides A-C, cytotoxic δ-elemanolide-type sesquiterpene lactones from Zinnia grandiflora

Bashyal, B. P., McLaughlin, S. P., & A., A. (2006). Zinagrandinolides A-C, cytotoxic δ-elemanolide-type sesquiterpene lactones from Zinnia grandiflora. Journal of Natural Products, 69(12), 1820-1822.

PMID: 17190470;Abstract:

Three new δ-elemanolide-type sesquiterpene lactones, zinagrandinolides A-C (1-3), and the known δ-elemanolide 4 have been isolated by a bioassay-guided fractionation of a cytotoxic hexane extract of the aerial parts of Zinnia grandiflora. The structures of 1-3 were determined on the basis of high-resolution mass and NMR data. All compounds exhibited strong cytotoxicity against the cancer cell lines NCI-H460, MCF-7, SF-268, and MIA Pa Ca-2 and the normal human fibroblast cell type WI-38, but none showed significant selectivity. © 2006 American Chemical Society and American Society of Pharmacognosy.

Five new isocoumarins from Sonoran desert plant-associated fungal strains Paraphaeosphaeria quadriseptata and Chaetomium chiversii

M., E., Paranagama, P. A., & A., A. (2006). Five new isocoumarins from Sonoran desert plant-associated fungal strains Paraphaeosphaeria quadriseptata and Chaetomium chiversii. Tetrahedron, 62(36), 8439-8446.

Abstract:

Five new isocoumarins, paraphaeosphaerins A-C and chaetochiversins A and B, biogenetically related to monocillin I and radicicol, have been isolated from solid agar cultures of Paraphaeosphaeria quadriseptata and Chaetomium chiversii, two fungal strains living in association with the Sonoran desert plants, Opuntia leptocaulis and Ephedra fasciculata, respectively. A new chroman-4-one, aposphaerin C, was also isolated from P. quadriseptata. Their structures and stereochemistry were elucidated using a combination of ¹H and ¹³C homo- and hetero-nuclear 2D NMR techniques, ¹H NMR analysis of Mosher's esters, and chemical correlations. © 2006 Elsevier Ltd. All rights reserved.

Microbial transformation of amino- and hydroxyanthraquinones by Beauveria bassiana ATCC 7159

Zhan, J., & Gunatilaka, A. L. (2006). Microbial transformation of amino- and hydroxyanthraquinones by Beauveria bassiana ATCC 7159. Journal of Natural Products, 69(10), 1525-1527.

PMID: 17067178;Abstract:

Microbial biotransformation of four amino- and hydroxyanthraquinones catalyzed by Beauveria bassiana ATCC 7159 has been studied. Incubation of 1,2-diaminoanthraquinone (1) with B. bassiana ATCC 7159 afforded 1-amino-2-(4′-O-methyl-2β-N-D-glucopyranosylamino)anthraquinone (5) in a hitherto unprecedented biotransformation involving N-glycosylation of an amine. Biotransformation of 1-aminoanthraquinone (2) yielded 1-amino-2-(4′-O-methyl-2β-O-D-glucopyranosyloxy)anthraquinone (6) as a result of microbial hydroxylation of C-2 followed by 4′-O-methyl- glucosylation of the newly introduced hydroxyl group. 1,8-Dihydroxyanthraquinone (3) and 1,2-dihydroxyanthraquinone (4) afforded 8-hydroxy-1-(4′-O-methyl- 1β-O-D-glucopyranosyloxy)anthraquinone (7) and 1-hydroxy-2-(4′-O- methyl-2β-O-D-glucopyranosyloxy)anthraquinone (8), respectively, resulting from 4′-O-methyl-glucosylation of the existing hydroxyl groups of the substrates. The efficiency of these conversions suggests that microbial biotransformation reactions offer an attractive alternative to chemical 4′-O-methyl-glucosylation of amino- and hydroxyanthraquinones. © 2006 American Chemical Society and American Society of Pharmacognosy.

Leslie Gunatilaka