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

Valente, L. M., Gunatilaka, A. L., Kingston, D. G., & Pinto, A. C. (1994). Norcucurbitacin gentiobiosides from Fevillea trilobata. Journal of Natural Products, 57(11), 1560-1563.

PMID: 7853005;Abstract:

The new norcucurbitacin glycosides, andirobicin A gentiobioside [2], and andirobicin C gentiobioside [1], and the known fevicordin F gentiobioside [3], were isolated from the aqueous MeOH fraction of a liquid-liquid partition of the MeOH extract of the seeds of Fevillea trilobata. Their structures were determined by nmr and ms techniques.

von Bierberstein, P., Yaming, X., Gunatilaka, L., & R. Gruener, R. (2014). Biomass production and withaferin A synthesis by Withania somnifera grown in aeroponics and hydroponics. HortScience, 2014, 49, ., 49, 1506–1509.
Fernando, H., Gunatilaka, A., Kumar, V., Weeratunga, G., Tezuka, Y., & Kikuchi, T. (1988). Two new quinone-methides from cassine balae: Revised structure of balaenonol. Tetrahedron Letters, 29(3), 387-390.

Abstract:

The structure of balaenol, a new quinone-methide triterpene isolated from Cassine balae has been deduced as 1 and the structure of the previously isolated balaenonol has been revised as 2 from their spectral data including 2-D heteronuclear 1H13C shift correlated NMR spectra and n.O.e studies. © 1988.

Padumadasa, C., Xu, Y., Wijeratne, K., U'Ren, J., Arnold, E., & Gunatilaka, L. (2017). Cytotoxic and Non-Cytotoxic Metabolites from Teratosphaeria sp. FL2137, a Fungus Associated with Pinus clausa. Journal of Natural Products. doi:10.1021/acs.jnatprod.7b00838
M., E., Bashyal, B. P., Liu, M. X., Rocha, D. D., M., G., U'Ren, J. M., Gunatilaka, M. K., Arnold, A. E., Whitesell, L., & A., A. (2012). Geopyxins A-E, ent -Kaurane diterpenoids from endolichenic fungal strains geopyxis aff. majalis and Geopyxis sp. AZ0066: Structure-activity relationships of geopyxins and their analogues(1). Journal of Natural Products, 75(3), 361-369.

PMID: 22264149;PMCID: PMC3359839;Abstract:

Four new ent-kaurane diterpenoids, geopyxins A-D (1-4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3. The structures of 1-6 were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher's ester method. Methylation of 1-3, 5, and 6 gave their corresponding methyl esters 7-11. On acetylation, 1 and 7 yielded their corresponding monoacetates 12 and 14 and diacetates 13 and 15. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds 2, 7-10, 12, 14, and 15 showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds 7-9, 14, and 15 were found to activate the heat-shock response at similar concentrations. From a preliminary structure-activity perspective, the electrophilic α,β-unsaturated ketone carbonyl motif present in all compounds except 6 and 11 was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation. © 2012 The American Chemical Society and American Society of Pharmacognosy.