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

Molnar, I., Gunatilaka, L., & 7 co-authors, C. (2016). Diversity-Oriented Combinatorial Biosynthesis of Hybrid Polyketide Scaffolds from Azaphilone and Benzenediol Lactone Biosynthons. Organic Letters, 18, 1262-1265.
Gunatilaka, A. (1976). Thin-layer chromatography of N-nitrosamines. Journal of Chromatography A, 120(1), 229-233.
Sultanbawa, M. U., Wannigama, G. P., Bandaranayake, W. M., Kumar, V., A., A., Marikar, F. A., Balasubramaniam, S., & Arsecularatne, S. N. (1978). Chemical investigation of ceylonese plants. Part XXIX. A survey of plants of Sri Lanka (Ceylon) for alkaloids I. Journal of Natural Products, 41(6), 597-633.

Abstract:

Four hundred and sixty-four Sri Lanka plant species, including 170 endemic species, were screened for the occurrence of alkaloids. The plants represented 314 genera and 96 families, of which 49 were tropical families. Extractions were carried out by three different procedures, and the presence of alkaloids was determined by Mayer's test. Tlc of the crude extracts furnished the approximate number of alkaloids. Ninety-one species, inclusive of 27 endemic species, gave a positive Mayer's test. By means of tlc, 417 species were tested with Dragendorff's reagent, and 137 were found to be positive. Of the 214 species tested with iodoplatinate reagent, 89 gave a positive response. Of the alkaloid-containing species, 128, distributed among 42 families, had not been previously reported in the literature, to the best of our knowledge. These included 59 endemic species distributed among 25 families.

Xu, Y., Espinosa-Artiles, P., Liu, M. X., Arnold, A. E., & Gunatilaka, A. A. (2013). Secoemestrin D, a cytotoxic epitetrathiodioxopiperizine, and emericellenes A-E, five sesterterpenoids from Emericella sp. AST0036, a fungal endophyte of Astragalus lentiginosus1. Journal of natural products, 76(12), 2330-2336.

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.

Jarman, T. R., Gunatilaka, A., & Widdowson, D. A. (1975). Investigations on the biosynthesis of steroids and terpenoids. XI. The 24-methylene sterol 24(28)-reductase of Saccharomyces cerevisiae. Bioorganic Chemistry, 4(2), 202-211.

Abstract:

The microsomal fraction of Saccharomyces cerevisiae has been shown to catalyse the NADPH-dependent reduction of ergosta-5,7,22,24(28)-tetraen-3β-ol to ergosterol. This cell-free system together with whole-cell cultures of polyene-resistant mutants has been used to compare the rates of reduction of other 24-methylene sterols. The results indicate that the enzyme involved exhibits a marked specificity for ergosta-5,7,22,24(28)-tetraen-3β-ol and support the concept of a major terminal step in ergosterol biosynthesis. © 1975.