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

Bokel, M., Diyasena, M., Gunatilaka, A., Kraus, W., & Sotheeswaran, S. (1988). Canaliculatol, an antifungal resveratrol trimer from Stemonoporous canaliculatus. Phytochemistry, 27(2), 377-380.

Abstract:

A new resveratrol trimer, canaliculatol, has been isolated from the bark of Stemonoporus canaliculatus. Canaliculatol showed antifungal activity against the fungus, Cladosporium cladosporioides. The structure and stereochemistry of canaliculatol is reported in this paper. © 1988.

Heltzel, C. E., Gunatilaka, A. L., Glass, T. E., & Kingston, D. G. (1993). Furofuranonaphthoquinones: bioactive compounds with a novel fused ring system from crescentia cujete. Tetrahedron, 49(31), 6757-6762.

Abstract:

Bioassay-directed fractionation of the methyl ethyl ketone extract of Crescentia cujete yielded the naphthoquinones 1 and 2. Both compounds are cytotoxic, and 1 shows selective DNA-damaging activity against yeast. Detailed spectroscopic interpretation led to the assignment of the structures of 1 and 2 as 3-hydroxymethylfuro[3,2-b]naphtho[2,3-d]furan-5,10-dione and 9-hydroxy-3-hydroxymethylfuro[3,2-b]naphtho[2,3-d]furan-5,10-dione, respectively. This is the first report of this fused furofuran ring system, either as a natural product or a synthetic substance. © 1993.

A., A., & Uvais, M. (1973). Chemical investigation of ceylonese plants. Part III. Extractives of the fruits of argyreia populifolia choisy (Convolvulaceae). Journal of the Chemical Society, Perkin Transactions 1, 1155-1157.

Abstract:

From the light petroleum extractives of the fruits of Argyreia populifolia Choisy, friedelin, friedelan-3β-ol, octacosan1-ol, β-sitosterol, a new ester [stearyl 4-hydroxycinnamate (I)], and an unidentified ester have been isolated. Stearyl 4-methoxycinnamate (II) has been synthesised and shown to be identical with the methyl ether of the natural ester (I).

A., A. (2006). Natural products from plant-associated microorganisms: Distribution, structural diversity, bioactivity, and implications of their occurrence. Journal of Natural Products, 69(3), 509-526.

PMID: 16562864;PMCID: PMC3362121;Abstract:

A growing body of evidence suggests that plant-associated microorganisms, especially endophytic and rhizosphere bacteria and fungi, represent a huge and largely untapped resource of natural products with chemical structures that have been optimized by evolution for biological and ecological relevance. A diverse array of bioactive small molecule natural products has been encountered in these microorganisms. The structures of over 230 metabolites isolated and characterized from over 70 plant-associated microbial strains during the past four years are presented with information on their hosts, culture conditions, and biological activities. Some significant biological and ecological implications of their occurrence are also reviewed. © 2006 American Chemical Society and American Society of Pharmacognosy.

Chongming, W. u., A., A., McCabe, F. L., Johnson, R. K., Spjut, R. W., & G., D. (1997). Bioactive and other sesquiterpenes from Chiloscyphus rivularis. Journal of Natural Products, 60(12), 1281-1286.

PMID: 9463110;Abstract:

Bioassay-directed fractionation of the methyl ethyl ketone extract of Chiloscyphus rivularis yielded five new sesquiterpenes, 12- hydroxychiloscyphone (2), chiloscypha-2,7-dione (3), 12-hydroxychiloscypha- 2,7-dione (4), chiloscypha-2,7,9-trione (5), and rivulalactone (6) in addition to the known sesquiterpenes, 4-hydroxyoppositan-7-one (7), chiloscyphone (1), and isointermedeol (8). The structure and stereochemistry of rivulalactone, a novel trinorsesquiterpene, was confirmed by its synthesis starting from 1. Compound 2 showed selective bioactivity in our yeast-based DNA-damaging assay and cytotoxicity to human lung carcinoma cells.