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

Gunaherath, G. B., Gunatilaka, A., Sultanbawa, M. S., & Balasubramaniam, S. (1983). 1,2(3)-Tetrahydro-3,3′-biplumbagin: A naphthalenone and other constituents from Plumbago zeylanica. Phytochemistry, 22(5), 1245-1247.

Abstract:

The isolation of plumbagin, droserone, isoshinanolone and a new naphthalenone, 1,2(3)-tetrahydro-3,3′-biplumbagin is reported from the phenolic fract. © 1983.

Subramanian, B., Nakeff, A., Tenney, K., Crews, P., Gunatilaka, L., & Valeriote, F. (2006). A new paradigm for the development of anticancer agents from natural products. Journal of Experimental Therapeutics and Oncology, 5(3), 195-204.

PMID: 16528970;PMCID: PMC1693669;Abstract:

A novel pharmacology paradigm has been developed which quickly and efficiently moves prospective anticancer drugs from the discovery phase through pharmacology testing and into therapeutic trial assessment. Following discovery, the drug is first assessed in a clonogenic assay which determines the cytotoxic effect of different concentrations of the drug at 3 different exposure durations: 2h, 24h and continuous (168 h). Second, pharmacokinetic information is obtained in both plasma and tumor for the drug administered at the maximum tolerated dose given intravenously. The first study defines the time-concentration profile required to obtain a specific cell survival for the tumor cells; the second study determines the concentration-time profile that can be obtained in both plasma and tumor at the maximum tolerated dose of the drug. The integration of this information determines whether a successful therapeutic trial is possible. Only when a drug shows therapeutic efficacy is a proteomics-based mechanism of action study initiated. Two drugs have been assessed in this paradigm: salicortin and fascaplysin A. © 2006 Old City Publishing, Inc.

Zhan, J., Kamal, G., Wijeratne, E. K., & Gunatilaka, A. L. (2007). Asperpyrone D and other metabolites of the plant-associated fungal strain Aspergillus tubingensis. Phytochemistry, 68(3), 368-372.

PMID: 17150233;PMCID: PMC3361907;Abstract:

Bioactivity-guided fractionation of a cytotoxic extract of Aspergillus tubingensis, a fungal strain occurring in the rhizosphere of the Sonoran desert plant, Fallugia paradoxa, afforded a dimeric naphtho-γ-pyrone asperpyrone D, nine known naphtho-γ-pyrones, funalenone, and the cytotoxic cyclic penta-peptide, malformin A1. © 2006 Elsevier Ltd. All rights reserved.

Gunatilaka, L., Xu, Y., Wijeratne, K., Brooks, A. D., Henrich, C. J., Tewary, P., & Sayers, T. J. (2017). 17beta-Hydroxywithanolides as Sensitizers of Renal Carcinoma Cells to TRAIL–Induced Apoptosis: Structure–Activity Relationships. Journal of Medicinal Chemistry, 60, 3039-3051. doi:10.1021/acs.jmedchem.7b00069
Gunatilaka, A., Silva, A. D., Sotheeswaran, S., & Tillekeratne, L. M. (1982). Horsfieldin, a lignan and other constituents from Horsfieldia iryaghedhi. Phytochemistry, 21(11), 2719-2723.

Abstract:

A new lignan, horsfieldin [2-(3-hydroxy-4-methoxyphenyl)-6-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo(3,3,0)octane], d-asarinin, (-)-dihydrocubebin, dodecanoylphloroglucinol, myristic acid, trimyristin and sitosterol have been isolated and characterized from the hot methanol extract of Horsfieldia iryaghedhi seeds. The absolute configuration of the lignans and the chemotaxonomic significance of their occurrence is discussed. © 1982.