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

Gunatilaka, A. L., Da, V., Dagne, E., Hofmann, G. A., Johnson, R. K., McCabe, F. L., Mattern, M. R., & G., D. (1998). Limonoids showing selective toxicity to DNA repair-deficient yeast and other constituents of Trichilia emetica. Journal of Natural Products, 61(2), 179-184.

PMID: 9514005;Abstract:

Bioactivity-directed fractionation of the MeCOEt extract of Trichilia emetica (Meliaceae) resulted in the isolation of the limonoids nymania 1 (1), drageana 4 (3), trichilin A (4), rohituka 3 (5), and Tr-B (7) and the novel seco-A protolimonoid 8. Of these, nymania 1 and Tr-B showed selective inhibitory activity toward DNA repair-deficient yeast mutants. The isolation, structure elucidation, 13C NMR spectral assignments, and biological activities of these compounds are reported.

Phillips, W. R., Baj, N. J., A., A., & G., D. (1996). C-geranyl compounds from Mimulus clevelandii. Journal of Natural Products, 59(5), 495-497.

PMID: 8778239;Abstract:

Fractionation of the MeCOEt extract of Mimulus clevelandii yielded the novel 4-geranyl-5-hydroxy-2(3H)-benzofuranone (1) and the five known 6- geranylflavanones diplacone (2a), 3'-O-methyldiplacone (2b), diplacol (2c), mimulone (2d), and 3'-O-methyldiplacol (2e). 2D-NMR methods required revision of assignments for diplacone and diplacol and resolved the uncertainty in the site of methylation for the methyl ethers.

Gunatilaka, A. L., Xu, Y., Bunting, D. P., Liu, M. X., & Bandaranayake, H. A. (2016). 17β-Hydroxy-18-acetoxywithanolides from Aeroponically Grown Physalis crassifolia and Their Potent and Selective Antiproliferative Activity for Prostate Cancer Cells. Journal of Natural Products, 79, 821-830.

When cultivated under aeroponic growth conditions, Physalis crassifolia produced eleven new withanolides (1–11) and seven known withanolides (12–18) including those obtained from the wild-crafted plant. The structures of the new withanolides were elucidated by the application of spectroscopic techniques, and the known withanolides were identified by comparison of their spectroscopic data with those reported. Withanolides 1–11 and 16 were evaluated for their potential anticancer activity using five tumor cell lines. Of these, the 17-hydroxy-18-acetoxywithanolides 1, 2, 6, 7, and 16 showed potent antiproliferative activity, with some having selectivity for prostate adenocarcinoma (LNCaP and PC-3M) compared to the breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460), and CNS glioma (SF-268) cell lines used. The cytotoxicity data obtained for 12–15, 17, and 19 have provided additional structure-activity relationship information for the 17-hydroxy-18-acetoxywithanolides.

Bandara, B. R., Gunatilaka, A. L., Wijeratne, E. K., & Adikaram, N. K. (1988). Antifungal constituents of Limonia acidissima. Planta Medica, 54(4), 374-375.