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, K., Oliviera, M., Mafazoli, J., Xu, Y., Minguzzi, S., Batista, P., Pessoa, O., Whitesell, L., & Gunatilaka, L. (2017). Withaferin A and Withanolide D Analogues with Dual Heat-Shock-Inducing and Cytotoxic Activities: Semisynthesis and Biological Evaluation. Journal of Natural Products.
Gunatilaka, A. L., Nanayakkara, N. D., & Uvais, M. (1979). Irradiation of friedelan-21-ones: Structure determination of novel friedelane triterpenes from kokoona zeylanica. Journal of the Chemical Society, Chemical Communications, 434-436.

Abstract:

Formation of the photoproducts (10) and (12) and chemical and spectroscopic evidence suggest that kokoononol obtained from Kokoona zeylanica is 27-hydroxyfriedelane-3,21-dione (1); kokoondiol and kokoonol have been identified as 21α,27-dihydroxyfriedelan-3-one (2) and 27-hydroxyfriedelan- 3-one (3), respectively, by chemical conversions.

A., A., Ramdayal, F. D., Sarragiotto, M. H., G., D., Sackett, D. L., & Hamel, E. (1999). Synthesis and biological evaluation of novel paclitaxel (Taxol) D-ring modified analogues. Journal of Organic Chemistry, 64(8), 2694-2703.

Abstract:

The semisynthesis and biological activity of paclitaxel (Taxol) analogues in which the oxygen atom in ring D is substituted by a sulfur or a selenium atom is presented. These derivatives were synthesized and tested in order to make more transparent the role of the oxetane ring in the biological activity of paclitaxel. The sulfur derivatives were found to be less active than paclitaxel in biological assays, while the selenium derivative could not be converted to its 4-acyl analogue. The results with the sulfur analogues suggest that the oxygen atom in the oxetane ring plays an important role in the mechanism by which paclitaxel exhibits its anticancer activity.

Liang, J., Huang, K., & Gunatilaka, A. L. (1998). A new 1,2-deoxytaxane diterpenoid from Taxus chinensis. Planta Medica, 64(2), 187-188.

PMID: 17253235;Abstract:

The bark of Taxus chinensis yielded a new taxane diterpenoid, 2- deacetoxy-7,9-dideacetyltaxinine J (1) together with several known taxoids. 1H- and 13C-NMR data of 1 are reported.

Carbonezi, C. A., Hamerski, L., A., A., Cavalheiro, A., Castro-Gamboa, I., Helena, D., Furlan, M., Claudia, M., Lopes, M. N., & Da, V. (2007). Bioactive flavone dimers from Ouratea multiflora (Ochnaceae). Brazilian Journal of Pharmacognosy, 17(3), 319-324.

Abstract:

Chromatographic fractionation of the organic extract from leaves of Ouratea multiflora afforded the flavone dimers heveaflavone, amentoflavone-7′, 4‴-dimethyl eter, podocarpusflavone-A and amentoflavone. Their structures were elucidated from spectral data, including 2D-NMR experiments of the natural substances. Biological activities of all isolates were evaluated, using antimicrobial assay against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, cytotoxicity assay against mouse lymphoma (L5178) and KB cell lines, TLC screening for acetylcholinesterase inhibitors and antioxidant activity measured by DPPH test.