[Nitrobenzofuroxane derivatives as dual action hiv-1 inhibitors]. / Proizvodnye nitrobenzofuroksanov v kachestve ingibitorov VICh-1 dvoinogo deistviia.

Human immunodeficiency virus first type (HIV-1) is a main cause of one of the most dangerous diseases, AIDS. The search for new inhibitors of the virus still remains an urgent task. One approach to suppress the HIV infection is to use a double-acting inhibitors, i.e. inhibitors directed to two stages of the viral life cycle. The catalytic domain of HIV-1 integrase has a similar spatial organization with ribonuclease (RNase H) domain of HIV-1 reverse transcriptase, and approach aimed to create HIV-1 integrase and RNase H double-acting is very promising. In this work we synthesized a series of 6-nitrobenzofuroxane derivatives and studied their ability to inhibit two viral enzymes - integrase and RNase H HIV-1.

Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors.

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.