Structure, stereochemistry, and biological activity of integramycin, a novel hexacyclic natural product produced by Actinoplanes sp that inhibits HIV-1 integrase

[GRAPHICS] HIV-1 integrase is a critical enzyme for viral replication, and its inhibition is an emerging target for potential antiviral chemotherapy. We have discovered a novel inhibitor, integramycin, from screening of fermentation extracts using an in vitro assay. Integramycin possesses a hexacyclic ring system and exhibited an IC50 value of 4 muM against HIV-1 integrase (strand transfer). The isolation, structure elucidation, stereochemistry, conformation, and biological activity has been described.