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

Dhanabalasingham, B., Karunaratne, V., Tezuka, Y., Kikuchi, T., & A., A. (1996). Biogenetically important quinonemethides and other triterpenoid constituents of Salacia reticulata. Phytochemistry, 42(5), 1377-1385.

Abstract:

Phytochemical investigation of the outer root bark of Salacia reticulata var. β-diandra (Celastraceae) has resulted in the isolation of two novel quinonemethide triterpenoids (celastroloids), isoiguesterinol and 30- hydroxypristimerin, along with salacenonal, several known celastroloids and friedo-oleanane triterpenoids. Details of the structural elucidation and 1H and 13C NMR spectral assignments of these compounds are presented and their biogenetic significance is discussed.

Gamlath, C. B., Gunatilaka, A. L., Tezuka, Y., Kikuchi, T., & Balasubramaniam, S. (1990). Quinone-methide, phenolic and related triterpenoids of plants of Celastraceae: further evidence for the structure ofCelastranhydride. Phytochemistry, 29(10), 3189-3192.

Abstract:

Quinone-methide and phenolic triterpenoids of the root outer bark ofCelastrus paniculatus have been identified as celastrol, pristimerin, zeylasterone and zeylasteral whereas those ofKokoona reflexa root outer bark were pristimerin, zeylasterone and zeylasteral. Celastranhydride, an unusual triterpene anhydride isolated fromK. zeylanica was shown to be present inK. reflexa, Cassine balae andReissantia indica. Details of the isolation and structure elucidation of celastranhydride are presented along with the analysis of1H-detected heteronuclear multiple-bond multi-quantum correlation (HMBC) NMR spectrum which aided the confirmation of its structure. Extracts ofC. balae, Gymnosporia emarginata, Pleurostylia opposita andR. indica were found to contain quinone-methides but were devoid of phenolic triterpenoids. The biosynthetic and chemotaxonomic significance of the co-occurrence of these triterpenoids in Celastraceae is discussed. © 1990 Pergamon Press plc.

Kim, Y. C., Che, Q., A., A., & G., D. (1996). Bioactive steroidal alkaloids from Solanum umbelliferum. Journal of Natural Products, 59(3), 283-285.

PMID: 8882430;Abstract:

Bioassay-directed fractionation of the MeOH extract of Solanum umbelliferum afforded solasodine (1), O-acetylsolasodine (2), and solasodine 3-O-β-D-glucopyranoside (3). Alkaloids 1 and 2 exhibited significant activity toward DNA repair-deficient yeast mutants, whereas 3 and the synthetic analogues N-acetylsolasodine (4) and N,O-diacetylsolasodine (5) were found to be inactive. Compounds 2 and 3 are new natural products.

Lau, E. C., Mason, D. J., Eichhorst, N., Engelder, P., Mesa, C., Kithsiri Wijeratne, E. M., Gunaherath, G. M., Gunatilaka, A. A., La Clair, J. J., & Chapman, E. (2015). Functional chromatographic technique for natural product isolation. Organic & biomolecular chemistry, 13, 2255-2259.

Natural product discovery arises through a unique interplay between chromatographic purification and biological assays. Currently, most techniques used for natural product purification deliver leads without a defined biological action. We now describe a technique, referred to herein as functional chromatography, that deploys biological affinity as the matrix for compound isolation.

Gao, S., Xu, Y., Valeriote, F. A., & A., A. (2011). Pierreiones A - D, solid tumor selective pyranoisoflavones and other cytotoxic constituents from antheroporum pierrei. Journal of Natural Products, 74(4), 852-856.

PMID: 21452840;PMCID: PMC3371367;Abstract:

Bioassay-guided fractionation of a solid tumor selective extract of the leaves and twigs of Antheroporum pierrei acquired from the U.S. National Cancer Institute extract repository afforded four new pyranoisoflavones, pierreiones A-D (1-4), together with rotenone (5), 12a-hydroxyrotenone (6), and tephrosin (7). The structures of all new compounds were determined on the basis of their spectroscopic data, and the absolute configuration of 1 was assigned with the help of 1H NMR analysis of its Mosher's ester derivatives. Compounds 1 and 5-7 accounted for the majority of the biological activity in terms of either cytotoxicity and/or selective toxicity to solid tumor cell lines. Pierreiones A (1) and B (2) demonstrated solid tumor selectivity with minimal cytotoxicity, while pierreione C (3) exhibited no activity. © 2011 The American Chemical Society and American Society of Pharmacognosy.