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

Wijeratne, E. K., Turbyville, T. J., Fritz, A., Whitesell, L., & Gunatilaka, A. L. (2006). A new dihydroxanthenone from a plant-associated strain of the fungus Chaetomium globosum demonstrates anticancer activity. Bioorganic and Medicinal Chemistry, 14(23), 7917-7923.

PMID: 16904330;Abstract:

Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain, Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone, globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new xanthones, globosuxanthone C (3) and D (4), 2-hydroxyvertixanthone (5), and two known anthraquinones (6 and 7). The structures of the new compounds 1-4 were elucidated by NMR and MS techniques, and the relative stereochemistry of 1 was determined by X-ray crystallographic analysis. Of the compounds encountered, 1 was found to exhibit strong cytotoxicity against a panel of seven human solid tumor cell lines, disrupt the cell cycle leading to the accumulation of cells in either G2/M or S phase, and induce classic signs of apoptosis. © 2006 Elsevier Ltd. All rights reserved.

Gunatilaka, A. A., Dhanabalasingham, B., Paredes, L., Jakupovic, J., Bohlmann, F., & Adikaram, N. K. (1987). Microglossic acid an alicyclic diterpene and other consituents of Microglossa zeylanica. Phytochemistry, 26(8), 2408-2409.

Abstract:

The aerial parts of Microglossa zeylanica collected in Sri Lanka contained β-farnesene, squalene, dammadienyl acetate, caryophyllen-1,10-epoxide, 5,4′-dihydroxy-6,7,8,3′-tetramethoxyflavone, dehydrofalcarindiol and two new alicyclic diterpenes, microglossic acid and dihydromicroglossic acid. Their structures were elucidated by high field 1H NMR spectroscopy. © 1987.

Heltzel, C. E., A., A., Glass, T. E., G., D., Hoffmann, G., & Johnson, R. K. (1993). Bioactive furanonaphthoquinones from Crescentia cujete. Journal of Natural Products, 56(9), 1500-1505.

PMID: 8254347;Abstract:

Bioassay-directed fractionation of the MeCOEt extract of Crescentia cujete (Bignonaceae) resulted in the isolation of (2S,3S)-3-hydroxy-5,6-dimethoxydehydroiso-α-lapachone [1], (2R)-5,6-dimethoxydehydroiso-α-lapachone [2], (2R)-5-methoxydehydroiso-α-lapachone [3], 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [4], 5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione[5],2- isopropenylnaphtho[2,3-b]furan-4,9-dione [6], and 5-hydroxydehydroiso-α-lapachone [7]. Compounds 1-3 are new, and all compounds are bioactive, showing selective activity towards DNA-repair-deficient yeast mutants. The isolation, structure elucidation, and biological activities of these compounds are reported.

Herz, J. E., Gunatilaka, A., Sotheeswaran, S., & Torres, J. V. (1982). Esterification of acid chlorides with thallium and potassium salts of 19-norethisterone: Formation of 17-enol esters. Steroids, 40(3), 261-266.

PMID: 7184202;Abstract:

During the esterification of acid chlorides with thallium and potassium salts of 19-norethisterone, 17-enol esters were isolated. The enol esters are formed Via the intermediate, 4-estrene-3, 17-dione. © 1982.

Wijeratne, E. M., He, H., Franzblau, S. G., Hoffman, A. M., & Gunatilaka, A. A. (2013). Phomapyrrolidones A-C, antitubercular alkaloids from the endophytic fungus Phoma sp. NRRL 46751. Journal of natural products, 76(10), 1860-1865.

Three new alkaloids, phomapyrrolidones A-C (1-3), bearing a cyclopenta[b]fluorene ring system were isolated from the mycelium extract of the endophytic fungal strain Phoma sp. NRRL 46751, inhabiting Saurauia scaberrinae. Methylation of 1 afforded its N-methyl derivative 4. The planar structures and relative configurations of 1-4 were elucidated by extensive spectroscopic analysis. Phomapyrrolidones B (2) and C (3) exhibited weak antitubercular activity at subcytotoxic concentrations.