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

M., G., & A., A. (1983). Studies on terpenoids and steroids. Part 3. Structure and synthesis of a new phenolic D:A-friedo-24-noroleanane triterpenoid, zeylasterone, from Kokoona zeylanica. Journal of the Chemical Society, Perkin Transactions 1, 2845-2850.

Abstract:

Zeylasterone, the first of a novel series of natural phenolic nortriterpenes from Kokoona zeylanica (Celastraceae) and ' kokum soap ' has been shown to be 29-methyl hydrogen 2,3-dihydroxy-6-oxo-D:A-friedo-24-noroleana-1,3, 5(10),7-tetraene-23,29-dioate (3) on the basis of spectroscopic and chemical evidence. Trimethylzeylasterone (8) has been synthesized from pristimerin, a quinone methide present in K. zeylanica and ' kokum soap '. The biosynthetic importance of some triterpenoids of K. zeylanica is discussed.

Gamlath, C. B., Gunatilaka, A. L., Tezuka, Y., Kikuchi, T., & Balasubramaniam, S. (1990). Quinone-methide, phenolic and related triterpenoids of plants of Celastraceae: further evidence for the structure ofCelastranhydride. Phytochemistry, 29(10), 3189-3192.

Abstract:

Quinone-methide and phenolic triterpenoids of the root outer bark ofCelastrus paniculatus have been identified as celastrol, pristimerin, zeylasterone and zeylasteral whereas those ofKokoona reflexa root outer bark were pristimerin, zeylasterone and zeylasteral. Celastranhydride, an unusual triterpene anhydride isolated fromK. zeylanica was shown to be present inK. reflexa, Cassine balae andReissantia indica. Details of the isolation and structure elucidation of celastranhydride are presented along with the analysis of1H-detected heteronuclear multiple-bond multi-quantum correlation (HMBC) NMR spectrum which aided the confirmation of its structure. Extracts ofC. balae, Gymnosporia emarginata, Pleurostylia opposita andR. indica were found to contain quinone-methides but were devoid of phenolic triterpenoids. The biosynthetic and chemotaxonomic significance of the co-occurrence of these triterpenoids in Celastraceae is discussed. © 1990 Pergamon Press plc.

Jacobsen, N. E., Wijeratne, E. K., Corsino, J., Furlan, M., da, V., & Gunatilaka, A. L. (2008). Biomimetic synthesis of xuxuarines Eα and Eβ: Structure revision of Rzedowskia bistriterpenoids. Bioorganic and Medicinal Chemistry, 16(4), 1884-1889.

PMID: 18055208;Abstract:

Reaction of pristimerin with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted in a biomimetic-type coupling leading to xuxuarines Eα and Eβ and not the previously reported Rzedowskia bistriterpenoids I and II suggesting that the structures proposed for these natural products need revision. A product obtained in this reaction by an unusual Diels-Alder addition followed by retro-Diels-Alder-type elimination was characterized as pristimerin dicyanophenalenedione. Complete 1H, and 13C NMR spectral assignments of xuxuarines Eα and Eβ have been made by the application of 1D and 2D NMR techniques. © 2007 Elsevier Ltd. All rights reserved.

Gamlath, C. B., Gunatilaka, A. L., Tezuka, Y., & Kikuchi, T. (1988). The structure of celastranhydride: A novel triterpene anhydride of celastraceae. Tetrahedron Letters, 29(1), 109-112.

Abstract:

The structure of celastranhydride, a novel triterpene anhydride isolated from Kokoona zeylanica and present in Cassine balae and Reissantia indica, all of the family Celastraceae, has been deduced as 1 from its spectral data including 2-D heteronuclear 1H13C shift correlated NMR spectra. © 1988.

Gunatilaka, A., Balasubramaniam, S., & Kumar, V. (1979). 2,3-Dimethoxyxanthone from Hypericum mysorense. Phytochemistry, 18(1), 182-183.

Abstract:

Different parts of Hypericum mysorense have been examined for the presence of2,3-dimethoxyxanthone which comprised the major constituent of the timber. Presence of simple xanthones in this genus supports the classification of Hypericum in the subfamily Hypericoideae in Guttiferae. © 1979.