Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus

Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus Научная публикация

Журнал

Russian Chemical Bulletin
ISSN: 1066-5285 , E-ISSN: 1573-9171

Вых. Данные

Год: 2023, Том: 72, Номер: 1, Страницы: 239-247 Страниц : 9 DOI: 10.1007/s11172-023-3729-x

Ключевые слова

bispidine SARS-CoV-2 inhibition main viral protease 3CLpro molecular docking amides

Авторы

Dalinger A.I. ¹ , Baev D.S. ² , Yarovaya O.I. ² , Chirkova V.Yu. ³ , Sharlaeva E.A. ³ , Belenkaya S.V. ^4,5 , Shcherbakov D.N. ^3,5 , Salakhutdinov N.F. ² , Vatsadze S.Z. ⁶

Организации

1	Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991 Moscow, Russian Federation
2	N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrentieva, 630090 Novosibirsk, Russian Federation
3	Altai State University, 61 prosp. Lenina, 656049 Barnaul, Russian Federation
4	Novosibirsk State University,2 ul. Pirogova, 630090 Novosibirsk, Russian Federation
5	State Research Center of Virology and Biotechnology VECTOR, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 630559 Koltsovo, Novosibirsk region, Russian Federation
6	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation

Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC50 = 1.56±0.55 µmol L−1). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity (IC50 = 100±5.7µmol L−1) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.

Dalinger A.I. , Baev D.S. , Yarovaya O.I. , Chirkova V.Y. , Sharlaeva E.A. , Belenkaya S.V. , Shcherbakov D.N. , Salakhutdinov N.F. , Vatsadze S.Z.
Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
Russian Chemical Bulletin. 2023. V.72. N1. P.239-247. DOI: 10.1007/s11172-023-3729-x WOS РИНЦ

Далингер А.И. , Баев Д.С. , Яровая О.И. , Чиркова В.Ю. , Шарлаева Е.А. , Беленькая С.В. , Щербаков Д.Н. , Салахутдинов Н.Ф. , Вацадзе С.З.
Синтез несимметричных амидов N-бензилбиспидинола и изучение их ингибирующей активности по отношению к основной вирусной протеазе SARS-CoV-2
Известия Академии наук. Серия химическая.(RUSS CHEM B+). 2023. Т.2023. №1. С.239-247. РИНЦ

Поступила в редакцию:	25 мая 2022 г.
Принята к публикации:	20 июн. 2022 г.
Опубликована online:	14 февр. 2023 г.

Web of science	WOS:000933481700019
РИНЦ	60883604
OpenAlex	W4320736067