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. (1985). Studies on medicinal plants of sri lanka. part 14: toxicity of some traditional medicinal herbs. Journal of Ethnopharmacology, 13(3), 323-335.

PMID: 4058035;Abstract:

Seventy five medicinal plants of the traditional Ayurvedic pharmacopoeia of Sri Lanka have been screened chemically for alkaloids and pyrrolizidine alkaloids. Of these, Crotolaria juncea L. was found to contain pyrrolizidine alkaloids with biological effects consistent with pyrrolizidine alkaloid toxicity. Feeding trials in rats with three plants lacking pyrrolizidine alkaloids, namely Aegle marmelos (L.) Corr., Hemidesmus indicus (L.) Ait. F. and Terminalia chebula Retz. produced hepatic lesions which included central vein abnormalities while Terminalia chebula and Withania somnifera (L.) Dunal produced marked renal lesions. © 1985.

Wijeratne, E. K., B., L., Kikuchi, T., Tezuka, Y., A., A., & G., D. (1995). Cyathocaline, an azafluorenone alkaloid from Cyathocalyx zeylanica. Journal of Natural Products, 58(3), 459-462.

Abstract:

Bioactivity-guided fractionation of a MeOH extract of the stem bark of Cyathocalyx zeylanica afforded a moderately bioactive new azafluorenone alkaloid, cyathocaline, the structure of which was established as 5,7-dihydroxy-6-methoxy-1-methyl-4-azafluoren-9-orie [1] with the aid of spectroscopic data.

Falsey, R. R., Marron, M. T., M., G., Shirahatti, N., Mahadevan, D., A., A., & Whitesell, L. (2006). Actin microfilament aggregation induced by withaferin A is mediated by annexin II. Nature Chemical Biology, 2(1), 33-38.

PMID: 16408090;Abstract:

The actin cytoskeleton supports diverse cellular processes such as endocytosis, oriented growth, adhesion and migration1. The dynamic nature of the cytoskeleton, however, has made it difficult to define the roles of the many accessory molecules that modulate actin organization, especially the multifunctional adapter protein annexin II (refs. 2,3). We now report that the compound withaferin A (1) can alter cytoskeletal architecture in a previously unknown manner by covalently binding annexin II and stimulating its basal F-actin cross-linking activity. Drug-mediated disruption of F-actin organization is dependent on annexin II expression by cells and markedly limits their migratory and invasive capabilities at subcytotoxic concentrations. Given the extensive ethnobotanical history of withaferin-containing plant preparations in the treatment of cancer and inflammatory and neurological disorders, we suggest that annexin II represents a feasible, previously unexploited target for therapeutic intervention by small-molecule drugs4. © 2005 Nature Publishing Group.

Gunatilaka, L. -., Wanigasekara, W. M., Wijeratne, E. M., & Arnold, A. E. (2013). 10'-Deoxy-10'a-hydroxyascochlorin, a New Cell Migration Inhibitor and Other Metabolites from Acremonium sp., a Fungal Endophyte in Ephedra trifurca. Natural Product Communications, 8, 601-604.
Wei, H., Xu, Y., Espinosa-Artiles, P., Liu, M. X., Luo, J., U'Ren, J. M., Arnold, A. E., & Gunatilaka, A. A. (2015). Sesquiterpenes and other constituents of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp. Phytochemistry, 118, 102-8.

Oxygenated guaiane-type sesquiterpenes, xylaguaianols A-D (1-4), an iso-cadinane-type sesquiterpene isocadinanol A (5), and an α-pyrone 9-hydroxyxylarone (6), together with five known sesquiterpenes (7-11), and four known cytochalasins (12-15) were isolated from a culture broth of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp. The structures of all compounds were elucidated by the analysis of their spectroscopic data and relative configurations of 1-5 were determined with the help of NMR NOESY experiments. Cytochalasins C (12), D (13), and Q (14) were investigated for their cytotoxic activity against five tumor cell lines. Cytochalasin D showed significant cytotoxicity against all five cell lines, with IC50s ranging from 0.22 to 1.44 μM, whereas cytochalasins C and Q exhibited moderate, but selective cytotoxicity.