Research output: Contribution to journal › Article › peer-review
(+)-fenchol and (−)-isopinocampheol derivatives targeting the entry process of filoviruses. / Sokolova, Anastasiya S.; Baev, Dmitriy S.; Mordvinova, Ekaterina D. et al.
In: European Journal of Medicinal Chemistry, Vol. 275, 116596, 05.09.2024.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - (+)-fenchol and (−)-isopinocampheol derivatives targeting the entry process of filoviruses
AU - Sokolova, Anastasiya S.
AU - Baev, Dmitriy S.
AU - Mordvinova, Ekaterina D.
AU - Yarovaya, Olga I.
AU - Volkova, Natalia V.
AU - Shcherbakov, Dmitriy N.
AU - Okhina, Alina A.
AU - Rogachev, Artem D.
AU - Shnaider, Tatiana A.
AU - Chvileva, Anastasiya S.
AU - Nikitina, Tatiana V.
AU - Tolstikova, Tatyana G.
AU - Salakhutdinov, Nariman F.
N1 - This work was supported by grant No. 22-73-00168 from the Russian Science Foundation. The authors would like to acknowledge the Multi-Access Chemical Research Center SB RAS for spectral and analytical measurements. The cultivation of human adult fibroblasts was performed at the multi-access center Collection of Pluripotent Human and Mammalian Cell Cultures for Biological and Biomedical Research at the ICG SB RAS (https://ckp.icgen.ru/cells/; http://www.biores.cytogen.ru/brc_cells/collections/ICG_SB_RAS_CELL). The microscopic analysis was conducted at the Multi-Access Center for Microscopy of Biological Subjects (ICG SB RAS, Novosibirsk, Russia). The MD simulations were performed with support from the Ministry of Science and Higher Education of the Russian Federation within a government contract for SRF SKIF and Boreskov Institute of Catalysis (project FWUR-2024-0040). The English language was corrected and certified by shevchuk-editing.com. This work was supported by grant No. 22-73-00168 from the Russian Science Foundation. The authors would like to acknowledge the Multi-Access Chemical Research Center SB RAS for spectral and analytical measurements. The cultivation of human adult fibroblasts was performed at the multi-access center Collection of Pluripotent Human and Mammalian Cell Cultures for Biological and Biomedical Research at the ICG SB RAS ( https://ckp.icgen.ru/cells/ ; http://www.biores.cytogen.ru/brc_cells/collections/ICG_SB_RAS_CELL ). The microscopic analysis was conducted at the Multi-Access Center for Microscopy of Biological Subjects (ICG SB RAS, Novosibirsk, Russia). The MD simulations were performed with support from the Ministry of Science and Higher Education of the Russian Federation within a government contract for SRF SKIF and Boreskov Institute of Catalysis (project FWUR-2024-0040). The English language was corrected and certified by shevchuk-editing.com
PY - 2024/9/5
Y1 - 2024/9/5
N2 - The increasing frequency of filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (−)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent antiviral compounds, with half-maximal inhibitory concentration (IC50) 1.4–20 μМ against Lenti-EboV-GP infection and 11.3–47 μМ against Lenti-MarV-GP infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the antiviral activity may be due to dual effects. This study offers new antiviral agents that are worthy of further exploration.
AB - The increasing frequency of filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (−)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent antiviral compounds, with half-maximal inhibitory concentration (IC50) 1.4–20 μМ against Lenti-EboV-GP infection and 11.3–47 μМ against Lenti-MarV-GP infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the antiviral activity may be due to dual effects. This study offers new antiviral agents that are worthy of further exploration.
KW - Ebola virus
KW - Fenchol
KW - Glycoprotein
KW - Isopinocampheol
KW - Lysosomotropic compounds
KW - Marburg virus
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85196192293&origin=inward&txGid=f95a6084360124c4c559c80a060314af
UR - https://www.mendeley.com/catalogue/0f7530d4-1c56-34aa-8dab-86d9afc430d3/
U2 - 10.1016/j.ejmech.2024.116596
DO - 10.1016/j.ejmech.2024.116596
M3 - Article
C2 - 38889610
VL - 275
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
M1 - 116596
ER -
ID: 60814842