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., Wijeratne, E. K., Faeth, S. H., & Gunatilaka, A. L. (2005). Globosumones A-C, cytotoxic orsellinic acid esters from the sonoran desert endophytic fungus Chaetomium globosum. Journal of Natural Products, 68(5), 724-728.

PMID: 15921417;Abstract:

Three new esters of orsellinic acid, globosumones A-C (1-3), and three known compounds, orsellinic acid (4), orcinol, and trichodion (5), were isolated from Chaetomium globosum endophytic on Ephedra fasciculata (Mormon tea). The structures of the new compounds 1-3 were established spectroscopically, which included 2D NMK experiments and 1H NMK studies on Mosher's ester derivatives. All compounds were evaluated for inhibition of cell proliferation in a panel of four cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), SF-268 (CNS glioma), and MIA Pa Ca-2 (pancreatic carcinoma), and normal human fibroblast cells (WI-38). Only globosumones A (1) and B (2) were found to be moderately active. © 2005 American Chemical Society and American Society of Pharmacognosy.

Wang, X., Bashyal, B. P., M., E., U'Ren, J. M., Liu, M. X., Gunatilaka, M. K., Arnold, A. E., & A., A. (2011). Smardaesidins -G, isopimarane and 20 nor-isopimarane diterpenoids from Smardaea sp., a fungal endophyte of the moss Ceratodon purpureus (1). Journal of Natural Products, 74(10), 2052-2061.

PMID: 21999655;PMCID: PMC3371368;Abstract:

Five new isopimarane diterpenes, smardaesidins -E (1- 5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7), together with sphaeropsidins A (8) and C-F (10-13) were isolated from an endophytic fungal strain, Smardaea sp. AZ0432, occurring in living photosynthetic tissue of the moss Ceratodon purpureus. Of these, smardaesidins B (2) and C (3) were obtained as an inseparable mixture of isomers. Chemical reduction of sphaeropsidin A (8) afforded sphaeropsidin B (9), whereas catalytic hydrogenation of 8 yielded 7-O-15,16-tetrahydrosphaeropsidin A (14) and its new derivative, 7-hydroxy-6-oxoisopimara-7-en-20-oic acid (15). The acetylation and diazomethane reaction of sphaeropsidin A (8) afforded two of its known derivatives, 6-O-acetylsphaeropsidin A (16) and 8,14-methylenesphaeropsidin A methyl ester (17), respectively. Methylation of 10 yielded sphaeropsidin C methyl ester (18). The planar structures and relative configurations of the new compounds 1-7 and 15 were elucidated using MS and 1D and 2D NMR experiments, while the absolute configurations of the stereocenters of 4 and 6-8 were assigned using a modified Mosher's ester method, CD spectra, and comparison of specific rotation data with literature values. Compounds 1-18 were evaluated for their potential anticancer activity using several cancer cell lines and cells derived from normal human primary fibroblasts. Of these, compounds 8, 11, and 16 showed significant cytotoxic activity. More importantly, sphaeropsidin A (8) showed cell-type selectivity in the cytotoxicity assay and inhibited migration of metastatic breast adenocarcinoma (MDA-MB-231) cells at subcytotoxic concentrations. © 2011 The American Chemical Society and American Society of Pharmacognosy.

Xu, Y., McLaughlin, S. P., & A., A. (2007). Sorbifolivaltrates A-D, diene valepotriates from Valeriana sorbifolia. Journal of Natural Products, 70(12), 2045-2048.

PMID: 18052324;Abstract:

Four new diene valepotriates, sorbifolivaltrates A-D (1-4), and the known compounds isovaltrate (5), valtrate (6), seneciovaltrate (7), valtrate hydrine B3 (8), and valtrate hydrine B7 (9), have been isolated by bioassay-guided fractionation of the cytotoxic hexanes and methyl ethyl ketone crude extracts of the aerial parts of Valeriana sorbifolia occurring in the Sonoran desert. The structures of 1-4 were determined on the basis of their high-resolution mass spectrometric and NMR spectroscopic data. All compounds exhibited weak to moderate cytotoxicity against the human metastatic prostate cancer cell line, PC-3M. © 2007 American Chemical Society and American Society of Pharmacognosy.

Dagne, E., Gunatilaka, A., Asmellash, S., Abate, D., Kingston, D. G., Hofmann, G. A., & Johnson, R. K. (1994). Two new cytotoxic cytochalasins from Xylaria obovata. Tetrahedron, 50(19), 5615-5620.

Abstract:

Two new cytotoxic cytochalasins were isolated by brine shrimp bioassay-guided fractionation from a culture of the wood inhabiting fungus, Xylaria obovata. Their structures were determined as 19,20-epoxycytochalasin Q (1) and its deacetyl analog 2 by the application of spectroscopic techniques and chemical correlation with cytochalasin R. Acetylation of 2 yielded 1. Both 1 and 2 were cytotoxic but were found to be inactive in an HIV-protease inhibitory assay and a mechanism-based DNA damaging yeast assay. © 1994.

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.