Synthesis and biological evaluation of novel antiviral agents as protein–protein interaction inhibitors

Abstract

In continuation of our research efforts toward the identification and optimization for novel inhibitors of interaction between human immunodeficiency virus type 1 integrase and cellular cofactor LEDGF/p75, we designed and synthesized a new series of 4-benzylindole derivatives. Most of the title compounds proved to be able to block this protein–protein interaction (PPI), with a percentage ranging from 30% to 90% at 100 µM. The most promising derivative was compound 10b showing IC₅₀ value of 6.41 µM. The main structure–activity relationships (SAR) are discussed and rationalized by docking studies.

• Docking studies
• HIV-1
• indoles
• LEDGF/p75
• synthesis