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

Arseculeratne, S. N., Gunatilaka, A., & Panabokke, R. G. (1981). Studies on medicinal plants of Sri Lanka: Occurrence of pyrrolizidine alkaloids and hepatotoxic properties in some traditional medicinal herbs. Journal of Ethnopharmacology, 4(2), 159-177.

PMID: 7311596;Abstract:

There is a paucity of data on the occurrence of hepatotoxic and hepatocarcinogenic pyrrolizidine alkaloids in medicinal plants, and there are no data on the hepatotoxic properties of herbal medicines that are used in the traditional pharmacopoiea of Sri Lanka and other Asian and African countries. In view of the extensive consumption of these herbs and the occurrence of chronic liver diseases including hepatocellular cancer in this and other countries of South Asia, we have screened fifty medicinal plants for pyrrolizidine alkaloids and have obtained positive results with three species, namely Crotalaria verrucosa L., Holarrhena antidysenterica (L.) Br., and Cassia auriculata L. Feeding trials in rats with materials from these three species produced liver lesions - disruption of the centrilobular veins, congestion or haemorrhage in the centrilobular sinusoids, centrilobular or focal hepatocellular necrosis - and histopathology in the lungs and kidneys which were compatible with the action of pyrrolizidine alkaloids. The presence of alkaloids in C. auriculata has not been previously reported nor has the presence of pyrrolizidine alkaloids in H. antidysenterica. It is suggested that the consumption of herbal medicines that contain pyrrólizidine alkaloids could contribute to the high incidence of chronic liver disease including primary hepatocellular cancer in Asian and African countries. © 1981.

Kang, M. J., Wu, T., Wijeratne, E. M., Lau, E. C., Mason, D. J., Mesa, C., Tillotson, J., Zhang, D. D., Gunatilaka, A. A., La Clair, J. J., & Chapman, E. (2014). Functional chromatography reveals three natural products that target the same protein with distinct mechanisms of action. Chembiochem : a European journal of chemical biology, 15(14), 2125-31.

Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1-hydroxydehydroherbarin, and phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high-throughput or phenotypic screening platforms.

G., A., Broughton, H. B., Attwood, S. V., & A., A. (1986). Two total syntheses of showdomycin and related studies. Journal of Organic Chemistry, 51(4), 495-503.

Abstract:

After a series of model reactions, D-ribose (2) was reacted with 3-(triphenylphosphoranylidene)-2,5-pyrrolidinedione (8a) in THF at reflux to produce 3(E)-(2(S),3(S),4(R),5-tetrahydroxy-1-pentylidene)-2,5-pyrrolidinedione (35) (75%). Subsequent cyclization of 35 using phenylselenenyl chloride followed by hydrogen peroxide gave showdomycin (1) (13%) and epi-showdomycin (36) (41%). Using a similar strategy 2,3-O-isopropylidene-D-ribose (37b) was reacted sequentially with 1-(triphenylmethyl)-3-(triphenylphosphoranylidene)-2,5-pyrrolidinedione (8b), phenylselenenyl chloride, hydrogen peroxide, and trifluoroacetic acid to give 1 (3% overall). © 1986 American Chemical Society.

Gunatilaka, A. A., Sultanbawa, U. S., Wimalasena, K., & Balasubramaniam, S. (1983). Studies on medicinal plants of Sri Lanka. 10. Linarin, a flavone glycoside from exacum macranthum. Planta Medica, 48(1), 61-62.
Tezuka, Y., Kikuchi, T., Dhanabalasingham, B., Karunaratne, V., & Gunatilaka, A. A. (1993). Salacenonal: A novel nortriterpenoid aldehyde of biogenetic significance from Salacia reticulata. Natural Product Letters, 3(4), 273-276.