Synthesis and evaluation of A-seco type triterpenoids for anti-HIV-1protease activity

2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC50 5.7 and 3.9 μM, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC50 15.7–88.1 μM). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c–3e, IC50 3.9–17.6 μM). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC50 > 80 μM). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors.

The 2,3-seco-dioic acid derivatives of different triterpene skeletons were prepared, two of which showed potent inhibitory activity against HIV-1 protease (3c and 3e). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced the activity against HIV-1 protease.Figure optionsDownload as PowerPoint slide