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

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

Журнал

Acta Naturae
ISSN: 2075-8251

Вых. Данные

Год: 2013, Том: 5, Номер: 1, Страницы: 63-72 Страниц : 10 DOI: 10.32607/20758251-2013-5-1-63-72

Авторы

Korolev S.P. ^1,2 , Kondrashina O.V. ^1,2 , Druzhilovsky D.S. ³ , Starosotnikov A.M. ⁴ , Dutov M.D. ⁴ , Bastrakov M.A. ⁴ , Dalinger I.L. ⁴ , Filimonov D.A. ³ , Shevelev S.A. ⁴ , Poroikov V.V. ³ , Agapkina Y.Y. ^1,2 , Gottikh M.B. ^1,2

Организации

1	Department of Chemistry, Lomonosov Moscow State University, Leninskie gory, 1/3, Moscow, Russia, 119991
2	Belozersky Research Institute of Physicochemical Biology, Lomonosov Moscow State University, Leniskie gory, 1/40, Moscow, Russia, 119991
3	Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya Str., 10/8, Moscow, Russia, 119121
4	Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Leninskiy prospekt, 47, Moscow, Russia, 119991

Human immunodeficiency virus type 1 integrase is one of the most attractive targets for the devel-opment 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 inhibi-tory 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.

Korolev S.P. , Kondrashina O.V. , Druzhilovsky D.S. , Starosotnikov A.M. , Dutov M.D. , Bastrakov M.A. , Dalinger I.L. , Filimonov D.A. , Shevelev S.A. , Poroikov V.V. , Agapkina Y.Y. , Gottikh M.B.
Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors
Acta Naturae. 2013. V.5. N1. P.63-72. DOI: 10.32607/20758251-2013-5-1-63-72 WOS Scopus OpenAlex

Web of science:	WOS:000334288000005
Scopus:	2-s2.0-84883772139
OpenAlex:	W35520510

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OpenAlex	22
Scopus	17
Web of science	20