Dammarenolic acid, a secodammarane triterpenoid from Aglaia sp shows potent anti-retroviral activity in vitro
Screening of a panel of purified compounds isolated from Aglaia spp. (Meliaceae) for inhibition of early steps in the lentiviral replication cycle led to the identification of the 3, 4-secodammarane triterpenoid, ignT1, which inhibited HIV-1 infection potently (IC50=0.48µg/ml), while cytotoxic effects and inhibition of cell proliferation were only observed at concentrations exceeding 10.69µg/ml. Time of addition experiments revealed similar kinetics to the non-nucleoside RT-inhibitor (NNRTI), Nevirapine, although the latter was significantly less cytotoxic. However, unlike Nevirapine, dammarenolic acid also potently inhibited the in vitro replication of other retroviruses, including Simian immunodeficiency virus and Murine leukemic virus in vector-based antiviral screening studies. Interestingly, the methyl ester analogue of dammarenolic acid, methyl dammarenolate had no anti-HIV-1 activity. Cell cycle analysis revealed that ignT1 arrests HeLa cells at the S and G2/M phase. These results strongly suggest that dammarenolic acid could be a promising lead compound for the development of novel anti-retrovirals.
Acknowledgements: The authors gratefully acknowledge the Postdoctoral Fellowship Awards to CS Nworu and CO Esimone by the Alexander von Humboldt Foundation
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