TY - JOUR

T1 - Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus

AU - Dalinger, A I

AU - Baev, D S

AU - Yarovaya, O I

AU - Chirkova, V Yu

AU - Sharlaeva, E A

AU - Belenkaya, S V

AU - Shcherbakov, D N

AU - Salakhutdinov, N F

AU - Vatsadze, S Z

N1 - This work was performed under fi nancial support of the Russian Foundation for Basic Research (Project No. 20-04-60215). Biological testing was carried out under fi nancial support of Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2021-1355 dated 12.10.2021) as part of the implementation of certain activities of the Federal Scientifi c and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure for 2019—2027. © Springer Science+Business Media LLC 2023.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - 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.

AB - 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.

KW - 3CLpro

KW - SARS-CoV-2

KW - amides

KW - bispidine

KW - inhibition

KW - main viral protease

KW - molecular docking

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85148451003&origin=inward&txGid=37e340c15b117449461ada1fdc7d0af8

UR - https://www.mendeley.com/catalogue/90187cc5-c76c-314a-8fe4-5ada7f3cef5b/

U2 - 10.1007/s11172-023-3729-x

DO - 10.1007/s11172-023-3729-x

M3 - Article

C2 - 36817558

VL - 72

SP - 239

EP - 247

JO - Russian Chemical Bulletin

JF - Russian Chemical Bulletin

SN - 1066-5285

IS - 1

ER -