Design, Synthesis, and Biological Evaluation of (+)‐Camphor‐ and (−)‐Fenchone‐Based Derivatives as Potent Orthopoxvirus Inhibitors

Design, Synthesis, and Biological Evaluation of (+)‐Camphor‐ and (−)‐Fenchone‐Based Derivatives as Potent Orthopoxvirus Inhibitors Full article

Journal

ChemMedChem
ISSN: 1860-7179 , E-ISSN: 1860-7187

Output data

Year: 2022, Volume: 17, Number: 12, Article number : e202100771, Pages count : 25 DOI: 10.1002/cmdc.202100771

Authors

Sokolova Anastasiya S. ¹ , Kovaleva Kseniya S. ¹ , Kuranov Sergey O. ¹ , Bormotov Nikolay I. ² , Borisevich Sophia S. ³ , Zhukovets Anastasiya A. ^1,4 , Yarovaya Olga I. ^1,4 , Serova Olga A. ² , Nawrozkij Maxim B. ⁵ , Vernigora Andrey A. ⁵ , Davidenko Andrey V. ⁵ , Khamitov Eduard M. ³ , Peshkov Roman Y. ⁴ , Shishkina Larisa N. ² , Maksuytov Rinat A. ² , Salakhutdinov Nariman F. ¹

Affiliations

1	Siberian Branch Russian Academy of Sciences N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry pr. Lavrent’ev 9, Novosibirsk, 630090 (Russia)
2	State Research Center of Virology and Biotechnology VECTOR Koltsovo, Novosibirsk Region 630559 (Russia)
3	Ufa Federal Research Centre of the Russian Academy of Sciences Ufa Institute of Chemistry pr. Oktyabrya 71, Ufa 450078 (Russia)
4	Novosibirsk State University Pirogova St. 1, Novosibirsk 630090 (Russia)
5	Volgograd State Technical University Lenina avenue 28, Volgograd 400005 (Russia)

In this work, a library of (+)-camphor and (−)-fenchone based N-acylhydrazones, amides, and esters, including para-substituted aromatic/hetaromatic/cyclohexane ring was synthesized, with potent orthopoxvirus inhibitors identified among them. Investigations of the structure-activity relationship revealed the significance of the substituent at the para-position of the aromatic ring. Also, the nature of the linker between a hydrophobic moiety and aromatic ring was clarified. Derivatives with p-Cl, p-Br, p-CF3, and p-NO2 substituted aromatic ring and derivatives with cyclohexane ring showed the highest antiviral activity against vaccinia virus, cowpox, and ectromelia virus. The hydrazone and the amide group were more favourable as a linker for antiviral activity than the ester group. Compounds 3 b and 7 e with high antiviral activity were examined using the time-of-addition assay and molecular docking study. The results revealed the tested compounds to inhibit the late processes of the orthopoxvirus replication cycle and the p37 viral protein to be a possible biological target.

Sokolova A.S. , Kovaleva K.S. , Kuranov S.O. , Bormotov N.I. , Borisevich S.S. , Zhukovets A.A. , Yarovaya O.I. , Serova O.A. , Nawrozkij M.B. , Vernigora A.A. , Davidenko A.V. , Khamitov E.M. , Peshkov R.Y. , Shishkina L.N. , Maksuytov R.A. , Salakhutdinov N.F.
Design, Synthesis, and Biological Evaluation of (+)‐Camphor‐ and (−)‐Fenchone‐Based Derivatives as Potent Orthopoxvirus Inhibitors
ChemMedChem. 2022. V.17. N12. e202100771 :1-25. DOI: 10.1002/cmdc.202100771 WOS Scopus РИНЦ

Submitted:	Dec 22, 2021
Accepted:	Apr 6, 2022
Published online:	Apr 6, 2022

Web of science	WOS:000789562000001
Scopus	2-s2.0-85128558751
Elibrary	48430399
OpenAlex	W4224282130