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

S. P. Korolev; Королев С. П.; O. V. Kondrashina; Кондрашина O. В.; D. S. Druzhilovsky; Дружиловский Д. С.; A. M. Starosotnikov; Старосотников A. M.; M. D. Dutov; Дутов M. Д.; M. A. Bastrakov; Бастраков M. A.; I. L. Dalinger; Далингер И. Л.; D. A. Filimonov; Филимонов Д. A.; S. A. Shevelev; Шевелев С. A.; V. V. Poroikov; Поройков В. В.; Y. Y. Agapkina; Агапкина Ю. Ю.; M. B. Gottikh; Готтих M. Б.

doi:10.32607/20758251-2013-5-1-63-72

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

Authors: 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
Affiliations:
1. Lomonosov Moscow State University
2. Belozersky Research Institute of Physicochemical Biology, Lomonosov Moscow State University
3. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
4. Zelinsky Institute of Organic Chemistry, Russian Academy of Science
Issue: Vol 5, No 1 (2013)
Pages: 63-72
Section: Research Articles
Submitted: 17.01.2020
Published: 15.03.2013
URL: https://actanaturae.ru/2075-8251/article/view/10605
DOI: https://doi.org/10.32607/20758251-2013-5-1-63-72
ID: 10605

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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.

Keywords

HIV-1 integrase, inhibition, nitrobenzofuroxan, nitrobenzofurazan, PASS, QikProp

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

Full Text

Abstract

Keywords

About the authors

S. P. Korolev

O. V. Kondrashina

D. S. Druzhilovsky

A. M. Starosotnikov

M. D. Dutov

M. A. Bastrakov

I. L. Dalinger

D. A. Filimonov

S. A. Shevelev

V. V. Poroikov

Y. Y. Agapkina

M. B. Gottikh

References

Supplementary files

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