Active site binding modes of dimeric phloroglucinols for HIV-1 reverse transcriptase, protease and integrase

Abstract

In a recent report on anti-HIV activity of dimeric phloroglucinol compounds, seven out of twenty one compounds were shown to possess good activity in HIV infected human CD4+ T cell line. The seven active compounds were docked into the active sites of HIV-1 reverse transcriptase (RT), integrase (IN), and protease (PR). Two compounds which have RT inhibitory activity exhibited H-bonding interaction with Lys101. Compounds 1, 5, and 6 exhibited good binding interactions with catalytic residues Asp64 and Asp116, while compounds 5 and 7 showed binding with PR (Asp25, Gly27, and Asp29). We propose here that compound 5 may be a dual inhibitor acting against both IN and PR. The docking results gave the information about active site binding modes of dimeric phloroglucinols interacting with HIV proteins.