Research output: Contribution to journal › Article › peer-review
Design, Synthesis, and Biological Evaluation of (+)-Camphor- and (−)-Fenchone-Based Derivatives as Potent Orthopoxvirus Inhibitors. / Sokolova, Anastasiya S.; Kovaleva, Kseniya S.; Kuranov, Sergey O. et al.
In: ChemMedChem, Vol. 17, No. 12, e202100771, 20.06.2022, p. e202100771.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Design, Synthesis, and Biological Evaluation of (+)-Camphor- and (−)-Fenchone-Based Derivatives as Potent Orthopoxvirus Inhibitors
AU - Sokolova, Anastasiya S.
AU - Kovaleva, Kseniya S.
AU - Kuranov, Sergey O.
AU - Bormotov, Nikolay I.
AU - Borisevich, Sophia S.
AU - Zhukovets, Anastasiya A.
AU - Yarovaya, Olga I.
AU - Serova, Olga A.
AU - Nawrozkij, Maxim B.
AU - Vernigora, Andrey A.
AU - Davidenko, Andrey V.
AU - Khamitov, Eduard M.
AU - Peshkov, Roman Y.
AU - Shishkina, Larisa N.
AU - Maksuytov, Rinat A.
AU - Salakhutdinov, Nariman F.
N1 - Funding Information: The authors acknowledge the Multi‐Access Chemical Service Centre SB RAS for spectral and analytical measurements. This work has been supported by a Russian Foundation for Basic Research (RFBR) Grant 20–33‐70067 and the State assignment of State Research Centre of Virology and Biotechnology VECTOR. The study of search for potential binding site were provided by financial support of the Ministry of Education and Science of the Russian Federation (Establishment of the structure, composition and physicochemical properties of organic, bioorganic, polymer molecules and complex compounds by chromatography, mass spectrometry, IR, UV, EPR and NMR spectroscopy award no. 122031400282–9). The authors thank Nina I. Komarova for performing HPLC analysis. Publisher Copyright: © 2022 Wiley-VCH GmbH.
PY - 2022/6/20
Y1 - 2022/6/20
N2 - 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.
AB - 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.
KW - (+)-camphor
KW - (−)-fenchone
KW - orthopoxviruses inhibitors
KW - p37 envelope protein
KW - structure-activity relationship
UR - http://www.scopus.com/inward/record.url?scp=85128558751&partnerID=8YFLogxK
U2 - 10.1002/cmdc.202100771
DO - 10.1002/cmdc.202100771
M3 - Article
C2 - 35388614
AN - SCOPUS:85128558751
VL - 17
SP - e202100771
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
IS - 12
M1 - e202100771
ER -
ID: 35991896