title: Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors.
abstract: Human immunodeficiency virus type 1 integrase is one of the most attractive targets for the development of anti-HIV-1 inhibitors. The capacity of a series of 2,1,3-benzoxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) selected using the PASS software to inhibit the catalytic activity of HIV-1 integrase was studied in the present work. Only the nitro-derivatives of these compounds were found to display inhibitory activity. The study of the mechanism of inhibition by nitro-benzofurazans/benzofuroxans showed that they impede the substrate DNA binding at the integrase active site. These inhibitors were also active against integrase mutants resistant to raltegravir, which is the first HIV-1 integrase inhibitor approved for clinical use. The comparison of computer-aided estimations of the pharmacodynamic and pharmacokinetic properties of the compounds studied and raltegravir led us to conclude that these compounds show promise and need to be further studied as potential HIV-1 integrase inhibitors.
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University, Leninskie gory, 1/3, Moscow, Russia, 119991 ; Belozersky Research Institute of Physicochemical Biology, Lomonosov Moscow State University, Leniskie gory, 1/40, Moscow, Russia, 119991.
authors.forename: S P
authors.initials: SP
authors.lastname: Korolev
authors.forename: O V
authors.initials: OV
authors.lastname: Kondrashina
authors.forename: D S
authors.initials: DS
authors.lastname: Druzhilovsky
authors.forename: A M
authors.initials: AM
authors.lastname: Starosotnikov
authors.forename: M D
authors.initials: MD
authors.lastname: Dutov
authors.forename: M A
authors.initials: MA
authors.lastname: Bastrakov
authors.forename: I L
authors.initials: IL
authors.lastname: Dalinger
authors.forename: D A
authors.initials: DA
authors.lastname: Filimonov
authors.forename: S A
authors.initials: SA
authors.lastname: Shevelev
authors.forename: V V
authors.initials: VV
authors.lastname: Poroikov
authors.forename: Y Y
authors.initials: YY
authors.lastname: Agapkina
authors.forename: M B
authors.initials: MB
authors.lastname: Gottikh
keywords: HIV-1 integrase; PASS; QikProp; inhibition; nitrobenzofurazan; nitrobenzofuroxan
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