Planta Med 2013; 79 - P88
DOI: 10.1055/s-0033-1336530

Antileishmanial and Antimicrobial Clerodane Diterpenes from Polyalthia longifolia

J Zhang 1, SK Jain 1, MR Jacob 1, BL Tekwani 1, 2, CD Hufford 1, 3, I Muhammad 1
  • 1National Center for Natural Products Research, and Departments of
  • 2Pharmacology and
  • 3Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA

Polyalthia longifolia is an evergreen tree, native to India, used in Indian System of Medicine as febrifuge and tonic. The stem-bark extracts of this plant and its isolated compounds were reported previously for various biological activities, including antibacterial, antifungal and cytotoxic activities [1 – 3]. In our investigation, three clerodane diterpenes were isolated by bioassay-guided fractionation and identified as (-) kolavenic acid (1), 16α-hydroxycleroda-3,13(14)Z-diene-15,16-olide (2) and 16-oxocleroda-3,13(14)E-diene-15-oic acid (3), using 1H- and 13C NMR, as well as 2D NMR experiments. Compound 1 displayed antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) with IC50 values of 8.32 and 5.08 µg/mL, respectively, while compound 2 showed very weak activity against MRSA (IC50 18.95 µg/mL). On the other hand, compound 2 and its acetylation product (4) displayed antileishmanial activity with IC50 values of 4.50 and 3.60 µg/mL, respectively, against Leishmania donovani promastigote. Both compounds, 2 and 4, were also evaluated against L. donovani axenic amastigote and amastigote in THP1 macrophage cultures, where they displayed strong activities with IC50 values of < 1.60 and 2.34 µg/mL, and 2.34 and 3.72 µg/mL, respectively. The anticancer activity of these compounds was also evaluated.

Acknowledgements: The authors thank US Department of Defense CDMRP, grant No. W81XWH-09, the NIH, NIAID, Division of AIDS, grant No. AI 27094, and the USDA Agricultural Research Service Specific Cooperative Agreement No. 58 – 6408 – 02 – 1-612, for financial support. References: [1] Marthanda MM, Subramaniyam M, et al. (2005) Fitoterapia, 76: 336. [2] Stivigny C, Bailly C, et al. (2005) J Curr Med Chem Anticancer Agents, 5: 173. [3] Jain AK, Jain A, et al. (2006) Plant Arch, 2: 841.