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

A., A., Samaranayake, G., G., D., Hoffmann, G., & Johnson, R. K. (1992). Bioactive ergost-5-ene-3β, 7α-diol derivatives from Pseudobersama mossambicensis. Journal of Natural Products, 55(11), 1648-1654.

PMID: 1479381;Abstract:

Bioactivity-directed fractionation of the methyl ethyl ketone extract of Pseudobersama mossambicensis resulted in the isolation of ergosta-5,24(28)-diene-3β,7α-diol [1], 24,28-epoxyergost-5-ene-3β,7α-diol [2], and ergost-5-ene-3β,7α,24,28-tetraol [3]. All three sterols showed selective activity towards DNA repair-deficient yeast mutants. The sterol 1 also showed cytotoxicity towards wild-type P-388 murine leukemia cells. The isolation, structural elucidation, and biological activities of these sterols are reported. The sterol 3 is most probably an artifact formed from 2 during the isolation process.

Fernando, H. C., Gunatilaka, A. L., Tezuka, Y., & Kikuchi, T. (1989). Studies on terpenoids and steroids - 18 balaenonol, balaenol and isobalaendiol: Three new 14(15)-ene-quinone-methide triterpenoids from cassine balae. Tetrahedron, 45(18), 5867-5876.

Abstract:

The three new 14(15)-ene-quinone-methide triterpenoids, balaenonol, balaenol and isobalaendiol, isolated from Cassine balae have been shown to be 3,21β-dihydroxy-2,22-dioxo-3,5,7,10(1),14(15)-pentaen-(14→15)-D:A-friedo-24,29-dinoroleanane (1), 3,21β-dihydroxy-2-oxo-3,5,7,10(1),14(15)-pentaen-(14→15)-D:A-friedo-24,29-dinoroleanane (2) and 3,21β,22β-trihydroxy-2-oxo-3,5,7,10(1),14(15)-pentaen-(14→15)-D:A-friedo-24,30-dinoroleanane (3), respectively, on the basis of spectroscopic evidence. The possible biosynthetic origin of these 14(15)-ene-quinone-methides from pristimerin is discussed. © 1989.

Bandara, B., Gunatilaka, A., Wijeratne, E., & MacLeod, J. K. (1990). Acridone alkaloids and coumarins from Pleiospermium alatum. Phytochemistry, 29(1), 297-301.

Abstract:

The root bark of Pleiospermium alatum afforded five alkaloids, five coumarins, lupeol and stigmasterol. One of the acridones, 1,5,6-trihydroxy-2,3-dimethoxy-10-methyl-9-acridone is a new compound while another, 1-hydroxy-2,3,5,6-tetramethoxy-10-methyl-9-acridone, is a new natural product. Chemotaxonomic aspects of the occurrence of acridone and coumarins in Pleiospermium is discussed. Seselin, one of the coumarins encountered displayed significant antifungal activity against Cladosporium cladosporioides. © 1990.

H., D., Gunatilaka, A. L., Jarman, T. R., Widdowson, D. A., Bard, M., & Woods, R. A. (1975). Biosynthesis of terpenes and steroids. Part X. The sterois of some yeast mutants doubly defective in ergosterol biosynthesis. Journal of the Chemical Society, Perkin Transactions 1, 88-92.

PMID: 1094026;Abstract:

The sterols of six double mutants of Saccharomyces cerevisiae have been isolated and characterised, and the sterol distribution has been related to the biosynthetic pathway from zymosterol to ergosterol. Hitherto unknown ergosta-5,8-dien-3β-ol and cholesta-7,24-dien-3β-ol have been isolated and characterised.

Tezuka, Y., Kikuchi, T., Dhanabalasingham, B., Karunaratne, V., & A., A. (1994). Studies on terpenoids and steroids, 25. Complete 1H-and 13C-NMR spectral assignments of salaciquinone, a new 7-oxo-quinonemethide dinortriterpenoid. Journal of Natural Products, 57(2), 270-276.

Abstract:

A new 7-oxo-quinonemethide dinortriterpenoid, salaciquinone [1], and a known quinonemethide dinortriterpenoid, isoiguesterin [3], were isolated from the root bark of Salacia reticulata var. β-diandra (Celastraceae). The structure elucidation of salaciquinone was based on detailed 2D and nOe-difference nmr spectroscopy, leading to the complete assignment of the 1H-and 13C-nmr spectra and revision of some 1H-nmr spectral assignments made previously for the related 7-oxo-quinonemethide nortriterpenoid, dispermoquinone [2]. Complete 1H- and 13C-nmr spectral assignments of isoiguesterin were also made, also leading to revision of some 13C-nmr assignments previously made for this compound.