Chemistry and Structure−Activity Relationship of HIV-1 Integrase Inhibitor Integracide B and Related Natural Products

Abstract
Integracides, 4,4-dimethylergostane triterpenoids, are inhibitors of HIV-1 integrase, a critical enzyme in replication of HIV-1. The chemistry and structure-activity relationship of integracide B and related natural products are described. A charged group, e.g., a sulfate, carboxyl, or amino, is required for the HIV-1 integrase activity. These compounds showed HIV-1 integrase activity with IC(50) values in the range 4.8-15 muM and exhibited antiviral activity in a viral spread assay, but with only a small or no therapeutic window.