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

Bashyal, B. P., & A., A. (2010). Tricinonoic acid and tricindiol, two new irregular sesquiterpenes from an endophytic strain of Fusarium tricinctum. Natural Product Research, 24(4), 349-356.

PMID: 20221941;PMCID: PMC3105968;Abstract:

Two new rare irregular sesquiterpenes, tricinonoic acid (1) and tricindiol (2), and the known furanopyrrolidones, NG-391 (3) and NG-393 (4), have been isolated from an EtOAc extract of Fusarium tricinctum, a fungus endophytic in the root tissue of the Sonoran desert plant, Rumex hymenosepalus. The structures of 1 and 2 were elucidated on the basis of their high-resolution mass, 1D and 2D NMR spectroscopic data. A possible biosynthetic route to 1 and 2 from farnesyl diphosphate is proposed. © 2010 Taylor & Francis.

Tewary, P., Gunatilaka, L., & Sayers, T. (2017). Using natural products to promote caspase-8-dependent cancer cell death. Cancer Immunology Immunotherapy, 66, 223-231. doi:10.1007/s00262-016-1855-0
Wijeratne, E. M., Lankananda, B. D., Tezuka, Y., Nagaoka, T., & Gunatilaka, A. A. (2001). Dimeric aporphine alkaloids of Phoenicanthus obliqua from Sri Lanka. Journal of Natural Products, 64(11), 1465-1467.

PMID: 11720536;Abstract:

A new dimeric aporphine alkaloid, phoenicanthusine (1), and six known alkaloids were isolated from the stem bark of Phoenicanthus obliqua. The structure of 1 was elucidated by 1D (1H, 13C) and 2D (1H-1H COSY, HMQC, HMBC, and NOESY) NMR and HRMS studies. Phoenicanthusine represents the first example of a N-6-C-4′ and C-7-C-5′ linked dimeric aporphine alkaloid.

Da, V., Izumisawa, C. M., Claudia, M., M., L., G., D., & Gunatilaka, A. L. (1997). Iridoids from Tocoyena formosa. Phytochemistry, 46(2), 305-308.

Abstract:

The leaves of Tocoyena formosa afforded two antifungal iridoids α- and β-gardiol, and the new iridoids, mollugoside methyl ester and formosinoside. Formosinoside was characterized as its hexaacetyl derivative.

Paranagama, P. A., M., E., & A., A. (2007). Uncovering biosynthetic potential of plant-associated fungi: Effect of culture conditions on metabolite production by Paraphaeosphaeria quadriseptata and Chaetomium chiversii. Journal of Natural Products, 70(12), 1939-1945.

PMID: 18052326;Abstract:

In an attempt to uncover the biosynthetic potential of plant-associated fungi, the effect of culture conditions on metabolite production by Paraphaeosphaeria quadriseptata and Chaetomium chiversii was investigated. These studies indicated that the production of the major metabolites by P. quadriseptata differ when the water used to make the media was changed from tap water to distilled water. It resulted in the isolation of six new secondary metabolites, cytosporones F-I (1-4), quadriseptin A (5), and 5′-hydroxymonocillin III (6) together with monocillin III (7), a metabolite new to P. quadriseptata, in addition to monocillin I (8), a previously known metabolite from this organism. Aposphaerin B (9) encountered was suspected to be an artifact originating from cytosporone F (1). Incorporation of heavy metal ions to P. quadriseptata culture medium induced production of monocillin I (8) by this fungus. Cultivation of C. chiversii in liquid medium resulted in the isolation of chaetochromin A (12) as the major metabolite instead of radicicol (10), the major constituent of this organism when grown in a solid medium. Compounds 1-7 and 12 were evaluated for their potential to inhibit Hsp90 and antiproliferative activity toward the cancer cell lines NCI-H460, MCF-7, and SF-268. Only compounds 6, 7, and 8 exhibited significant activity in both assays. © 2007 American Chemical Society and American Society of Pharmacognosy.