Leslie Gunatilaka

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
Contact
(520) 621-9932

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

Zhan, J., & Gunatilaka, A. L. (2006). Selective 4′-O-methylglycosylation of the pentahydroxy-flavonoid quercetin by Beauveria bassiana ATCC 7159. Biocatalysis and Biotransformation, 24(5), 396-399.

Abstract:

Biotransformation of the pentahydroxy-flavonoid natural product, quercetin, by Beauveria bassiana ATCC 7159 afforded a new derivative, quercetin-4′-O-methyl-7-β-D-glucopyranoside, in 87% isolated yield suggesting that glucosylation of the substrate occurred with high selectivity at C-7-OH out of the five hydroxyl groups. Most of the product was isolated from the mycelium and the filtrate of the culture medium did not show any catalytic activity. The mycelium is capable of performing this biotransformation when suspended in buffers of pH 2.1 and 7.2, suggesting that intracellular enzymes are involved and that they are active at a wide range of extracellular pH.

Meade-Tollin, L. C., M., E., Cooper, D., Guild, M., Jon, E., Fritz, A., Zhou, G., Whitesell, L., Liang, J., & A., A. (2004). Ponicidin and Oridonin Are Responsible for the Antiangiogenic Activity of Rabdosia rubescens, a Constituent of the Herbal Supplement PC SPES. Journal of Natural Products, 67(1), 2-4.

PMID: 14738375;Abstract:

Antiangiogenic activity has been identified in an aqueous EtOH extract of Rabdosia rubescens, a component of the dietary supplement PC SPES. Bioassay-guided fractionation using a novel in vitro human endothelial cell-based assay for angiogenesis afforded the diterpenoids ponicidin (1) and oridonin (2), with significant antiangiogenic activity at subcytotoxic concentrations, suggesting that these constituents may strongly contribute to the demonstrated clinical efficacy of PC SPES as a treatment for advanced prostate cancer.

Gunatilaka, A. L., Uvais, M., Sultanbawa, S., Surendrakumar, S., & Somanathan, R. (1983). Structure of a bipyridine alkaloid from Broussonetia zeylanica. Phytochemistry, 22(12), 2847-2850.

Abstract:

From the benzene extract of the timber of Broussonetia zeylanica, 8-hydroxyquinoline-4-aldehyde, a new alkaloid and two unidentified minor alkaloids have been isolated. The spectroscopic evidence suggested the new alkaloid to be 3,4′-dihydroxy-2,3′-bipyridine. © 1983.

Yuquan, X. u., Wijeratne, E. K., Espinosa-Artiles, P., Gunatilaka, A. L., & Molnár, I. (2009). Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer depsipeptide cell migration inhibitors from Beauveria bassiana. ChemBioChem, 10(2), 345-354.

PMID: 19105175;Abstract:

Fungal cyclooligomer depsipeptides such as beauvericin, bassianolide, and enniatins display antibiotic, antifungal, insecticidal, broad-spectrum cancer cell antiproliferative, and cell migration inhibitory activities. We have identified a gene encoding a novel enzyme, ketoisovalerate reductase (KIVR), which is the sole provider of D-hydroxyisovalerate (D-Hiv), a common precursor for cyclooligomer depsipeptide biosynthesis in Beauveria bassiana. KIVR and related hypothetical oxidoreductases encoded in fungal genomes are similar to ketopantoate reductases but not to D-hydroxycarboxylate dehydrogenases. We demonstrate that a KIVR knockout B. bassiana strain can be used for the efficient mutasynthesis of unnatural beauvericin congeners. Simultaneous feeding of precursor analogues enabled the combinatorial mutasynthesis of scrambled beauvericins, some assembled entirely from unnatural precursors. The effects of the introduced structural changes on the antiproliferative and cell migration inhibitory ACHTUNGTRENNUNGactivities of these analogues were evaluated. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wijeratne, E. K., & Gunatilaka, A. L. (2011). Biomimetic conversion of (-)-fusoxypyridone and (-)-oxysporidinone to (-)-sambutoxin: Further evidence for the structure of the tricyclic pyridone alkaloid, (-)-fusoxypyridone. Bioorganic and Medicinal Chemistry Letters, 21(8), 2327-2329.

PMID: 21419624;PMCID: PMC3359017;Abstract:

Biomimetic-type reactions of the tricyclic pyridone alkaloid, (-)-fusoxypyridone [(-)-4,6′-anhydrooxysporidinone] (1), recently encountered in an endophytic strain of Fusarium oxysporum, and (-)-oxysporidinone (2) afforded (-)-sambutoxin (3) and an analogue of 1, identified as (-)-1′(6′)-dehydro-4,6′-anhydrooxysporidinone (4), thus confirming the structure previously proposed for 1 and suggesting that 1-3 bear the same relative stereochemistry. Oxidation of 4 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) yielded a hitherto unknown sambutoxin analogue, (-)-4,2′-anhydrosambutoxin (5). © 2011 Elsevier Ltd. All rights reserved.