Synthesis of conjugates of (a R,7 S)-colchicine with monoterpenoids and investigation of their biological activity

E S Shchegravina; S D Usova; D S Baev; E S Mozhaitsev; D N Shcherbakov; S V Belenkaya; E A Volosnikova; V Yu Chirkova; E A Sharlaeva; E V Svirshchevskaya; I P Fonareva; A R Sitdikova; N F Salakhutdinov; O I Yarovaya; A Yu Fedorov

doi:10.1007/s11172-023-3730-4

Synthesis of conjugates of (a R,7 S)-colchicine with monoterpenoids and investigation of their biological activity

Russ Chem Bull. 2023;72(1):248-262. doi: 10.1007/s11172-023-3730-4. Epub 2023 Feb 14.

Authors

Affiliations

¹ Lobachevsky State University of Nizhny Novgorod, k. 2, 23 prosp. Gagarina, 603950 Nizhny Novgorod, Russian Federation.
² N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Akad. Lavrent'eva, 630090 Novosibirsk, Russian Federation.
³ State Scientific Center of Virology and Biotechnology "Vector", 630559 Koltsovo, Novosibirsk Region, Russian Federation.
⁴ Novosibirsk State University, 1 ul. Pirogova, 630090 Novosibirsk, Russian Federation.
⁵ Altai State University, 61 Leninsky prosp., 656049 Barnaul, Russian Federation.
⁶ Department of Immunology, M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 ul. Miklukho-Maklaya, 117997 Moscow, Russian Federation.

Abstract

Conjugates of the natural alkaloid (aR,7S)-colchicine with bicyclic monoterpenoids and their derivatives were synthesized for the first time. Molecular docking of the synthesized agents in the active site of the main viral protease of the SARS-CoV-2 virus was carried out. The cytotoxic properties of the agents against different cell lines and the ability to inhibit the main viral protease 3CLPro were studied.

Keywords: SARS-Cov-2 3CLPro; antiproliferative activity; colchicine; molecular docking; monoterpenoids.