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
(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


Bashyal, B. P., Wellensiek, B. P., Ramakrishnan, R., Faeth, S. H., Ahmad, N., & Gunatilaka, A. A. (2014). Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi. Bioorganic & medicinal chemistry, 22(21), 6112-6.
BIO5 Collaborators
Nafees Ahmad, Leslie Gunatilaka

Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data. When tested in our cell-based assay at concentrations insignificantly toxic to T-cells, altertoxins V (1), I (3), II (4), and III (5) completely inhibited replication of the HIV-1 virus at concentrations of 0.50, 2.20, 0.30, and 1.50 μM, respectively. Our findings suggest that the epoxyperylene structural scaffold in altertoxins may be manipulated to produce potent anti-HIV therapeutics.

Wellensiek, B. P., Ramakrishnan, R., Bashyal, B. P., Eason, Y., Gunatilaka, A. A., & Ahmad, N. (2013). Inhibition of HIV-1 Replication by Secondary Metabolites From Endophytic Fungi of Desert Plants. The open virology journal, 7, 72-80.
BIO5 Collaborators
Nafees Ahmad, Leslie Gunatilaka

Most antiretroviral drugs currently in use to treat an HIV-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. However, a largely unexplored source for HIV-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. These fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. We prepared several hundred extracts from endophytic fungi of desert plants and evaluated the inhibitory effects on HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T-lymphocytes. Those extracts that inhibited viral replication were fractionated in order to isolate the compounds responsible for activity. Multiple rounds of fractionation and antiviral evaluation lead to the identification of four compounds, which almost completely impede HIV-1 replication. These studies demonstrate that metabolites from endophytic fungi of desert plants can serve as a viable source for identifying potent inhibitors of HIV-1 replication.

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.