JOURNAL OF MEDICINAL CHEMISTRY, vol.54, no.2, pp.572-579, 2011 (SCI-Expanded)
On the basis of our earlier molecular docking analysis, we designed and synthesized 5-((arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones (12a-o) as HIV-1 entry inhibitors. Compounds 12a-o effectively inhibited infection by both laboratory-adapted and primary HIV-1 strains and blocked HIV-1 mediated cell cell fusion and gp41 six-helix bundle formation. Molecular docking analyses on two highly active inhibitors, 12b, containing a carboxylic acid group, and 12m, containing a tetrazole group, indicated that they both fit snugly into the hydrophobic cavity of HIV-1 gp41 from which each has important ionic interactions with lysine 574 (K574). By contrast, molecular docking of 12i, a less active compound containing a pyrrole instead of a furan ring, indicated a completely different orientation from 12b and 12m and missed critical interactions.