Anti-HIV activity of semisynthetic derivatives of andrographolide and computational study of HIV-1 gp120 protein binding

Andrographolide, a diterpene lactone of the Andrographis paniculata, displays anti-HIV activity in vitro. A series of andrographolide derivatives have been synthesized and evaluated for their anti-HIV activity in a cell-free virus infectivity assay using TZM-bl cells. As compared to andrographolide, 3-nitrobenzylidene derivative 6 showed higher in vitro anti-HIV activity, whereas 2',6'-dichloro-nicotinoyl ester derivative 9 showed higher Therapeutic Index. The andrographolide and its derivatives, 6 and 9, inhibited gp120-mediated cell fusion of HL2/3 cells (expressing gp120 on its surface) with TZM-bl cells (expressing CD4 and co-receptors CCR5 & CXCR4). Further, computational studies revealed that these molecules bind to the important residues of V3 loop of gp120. These results suggest that andrographolide derivatives may be promising candidates for prevention of HIV infection. (C) 2012 Elsevier Masson SAS. All rights reserved.