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

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. Copyright 2010 Elsevier Ltd. All rights reserved.