title: 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.
authors.affiliation: Centre for Pharmacoinformatic, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, India.
authors.forename: Pawan
authors.initials: P
authors.lastname: Gupta
authors.forename: Rajender
authors.initials: R
authors.lastname: Kumar
authors.forename: Prabha
authors.initials: P
authors.lastname: Garg
authors.forename: Inder Pal
authors.initials: IP
authors.lastname: Singh
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D002460:Cell Line; D003198:Computer Simulation; D019281:Dimerization; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D010696:Phloroglucinol / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D010696:Phloroglucinol; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; C514801:p31 integrase protein, Human immunodeficiency virus 1