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., G., D., M., E., M., B., Hofmann, G. A., & Johnson, R. K. (1994). Biological activity of some coumarins from Sri Lankan Rutaceae. Journal of Natural Products, 57(4), 518-520.

PMID: 8021652;Abstract:

Twelve coumarins isolated from plants of the Rutaceae collected in Sri Lanka have been subjected to a mechanism-based anticancer bioassay employing DNA repair-deficient and repair-proficient yeasts. Of these, seselin [10] and xanthyletin [11] were found to be active. Seselin also exhibited moderate cytotoxicity.

Tezuka, Y., Kikuchi, T., Fernando, H., & Gunatilaka, A. (1993). 1H and 13C NMR spectral assignments of some ene-quinonemethide nortriterpenoids. Phytochemistry, 32(6), 1531-1534.

Abstract:

The 1H and 13C NMR spectra of three natural 14(15)-ene-quinonemethide nortriterpenoids, balaenonol, balaenol and isobalaendiol have been comple. © 1993.

Kamal, G. M., Gunaherath, B., & Gunatilaka, A. L. (1983). 23-oxo-isopristimerin III: A new natural phenolic (9+8)-24-nor-d:a-friedo-oleanan triterpene. Tetrahedron Letters, 24(27), 2799-2800.

Abstract:

The structure of a new natural phenolic (9+8)-24-nor-D:A-friedo-oleanan triterpene isolated from Kokoona zeylanica has been established as 23-oxo-isopristimerin III. © 1983.

Yuquan, X. u., Zhan, J., M., E., Burns, A. M., A., A., & Molnár, I. (2007). Cytotoxic and antihaptotactic beauvericin analogues from precursor-directed biosynthesis with the insect pathogen Beauveria bassiana ATCC 7159. Journal of Natural Products, 70(9), 1467-1471.

PMID: 17803266;Abstract:

Precursor-directed biosynthesis was used to produce analogues of the cyclic depsipeptide mycotoxin beauvericin (1) using the filamentous fungus Beauveria bassiana ATCC 7159. Feeding 30 analogues of D-2-hydroxyisovalerate and L-phenylalanine, the natural 2-hydroxycarboxylic acid and amino acid precursors of beauvericin, led to the biosynthesis of novel beauvericins. Six of these were isolated and characterized, and their cytotoxicity and directional cell migration (haptotaxis) inhibitory activity against the metastatic prostate cancer cell line PC-3M were evaluated. Replacement of one, two, or all three of the D-2-hydroxyisovalerate constituents in beauvericin (1) with 2-hydroxybutyrate moieties (beauvericins G1-3, compounds 2-4) caused a parallel decline of cell migration inhibitory activity and cytotoxicity, suggesting a requirement for a branched side chain for both of these biological activities at the corresponding positions of beauvericins. Replacement of one, two, or all three N-methyl-L-phenylalanine residues of beauvericin with N-methyl-L-3-fluorophenylalanine moieties (beauvericins H1-3, compounds 5-7) increased cytotoxicity without affecting antihaptotactic activity. © 2007 American Chemical Society and American Society of Pharmacognosy.

Luo, J., Wang, X., Xu, Y., U'Ren, J. M., Arnold, A. E., Kong, L., & Gunatilaka, A. A. (2014). Delitschiapyrone A, a pyrone-naphthalenone adduct bearing a new pentacyclic ring system from the leaf-associated fungus Delitschia sp. FL1581. Organic letters, 16(22), 5944-7.

Delitschiapyrone A (1), an α-pyrone-naphthalenone adduct with an unprecedented pentacyclic ring system, was isolated from a solid culture of the leaf-associated fungus Delitschia sp. FL1581. The structure of 1 was elucidated by spectroscopic analysis and X-ray crystallography, and its absolute configuration was defined by experimental and calculated ECD. Biosynthetically, the unique 6/6/5/7/6 pentacyclic core of 1 may be formed by an intermolecular Diels-Alder-type addition of the precursors derived from (1'R)-2',3'-dihydropyrenocine C (2) and 6-ethyl-2,7-dimethoxyjuglone (3) found to co-occur with 1 in this fungus.