Antileishmanial and Antimicrobial Clerodane Diterpenes from Polyalthia longifolia

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.