Research output: Contribution to journal › Article › peer-review
Discovery of monoterpenoid-based benzamides bearing bicyclo[2.2.1]heptane motif as influenza H1N1 virus inhibitors. / Sokolova, Anastasiya S.; Samsonova, Valeria V.; Kuranov, Sergey O. et al.
In: Bioorganic and Medicinal Chemistry, Vol. 135, 118555, 04.2026.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Discovery of monoterpenoid-based benzamides bearing bicyclo[2.2.1]heptane motif as influenza H1N1 virus inhibitors
AU - Sokolova, Anastasiya S.
AU - Samsonova, Valeria V.
AU - Kuranov, Sergey O.
AU - Yarovaya, Оlga I.
AU - Rogachev, Artem D.
AU - Esaulkova, Iana L.
AU - Volobueva, Alexandrina S.
AU - Zarubaev, Vladimir V.
AU - Salakhutdinov, Nariman F.
N1 - Discovery of monoterpenoid-based benzamides bearing bicyclo[2.2.1]heptane motif as influenza H1N1 virus inhibitors / A. S. Sokolova, V. V. Samsonova, S. O. Kuranov [et al.] // Bioorganic & Medicinal Chemistry. – 2026. – Vol. 135. – P. 118555. – DOI 10.1016/j.bmc.2026.118555. – EDN IVBSBX. The chemical part of the work was carried out with the support by the Ministry of Science and Higher Education of the Russian Federation within the governmental order for N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS (project FWUE-2025-0006). The authors would like to acknowledge the Multi-Access Chemical Research Center SB RAS for spectral and analytical measurements. The virologyrelated part of the study was realized within the govermental order for St. Petersburg Pasteur Institute (project 121030200272-6, adopted Mar 02, 2021).
PY - 2026/4
Y1 - 2026/4
N2 - The persistent threat of influenza pandemics and the limitations of existing therapies necessitate the discovery of novel antiviral agents. This study investigates a series of monoterpenoid-based benzamides, derived from natural products (+)-camphor and (−)-fenchone, as a new class of inhibitors against influenza A virus (IAV). Building upon previous findings of their activity against orthopoxviruses, we identified several derivatives with potent activity against the A/H1N1 strain. Structure-activity relationship (SAR) analysis revealed that antiviral efficacy is critically dependent on the substituent's nature and position on the aromatic ring, the stereochemistry of the bicyclo[2.2.1]heptane core, and the amide configuration. Key lead compounds demonstrated significant inhibitory activity against the A/Puerto Rico/8/34 (H1N1) strain with high selectivity, and one derivative also showed promising activity against the highly pathogenic A(H7N9) strain. A representative compound demonstrated high metabolic stability in murine blood in vitro and exhibited promising pharmacokinetic properties in vivo following intragastric administration in mice. Mechanistic studies revealed two distinct profiles: one subset of inhibitors likely targets viral entry, while another appears to interfere with a later stage, such as assembly; their action is not mediated by neuraminidase inhibition. These findings establish monoterpenoid benzamides bearing the bicyclo[2.2.1]heptane motif as a promising scaffold for the development of anti-influenza agents, warranting further investigation into their precise molecular target and in vivo efficacy.
AB - The persistent threat of influenza pandemics and the limitations of existing therapies necessitate the discovery of novel antiviral agents. This study investigates a series of monoterpenoid-based benzamides, derived from natural products (+)-camphor and (−)-fenchone, as a new class of inhibitors against influenza A virus (IAV). Building upon previous findings of their activity against orthopoxviruses, we identified several derivatives with potent activity against the A/H1N1 strain. Structure-activity relationship (SAR) analysis revealed that antiviral efficacy is critically dependent on the substituent's nature and position on the aromatic ring, the stereochemistry of the bicyclo[2.2.1]heptane core, and the amide configuration. Key lead compounds demonstrated significant inhibitory activity against the A/Puerto Rico/8/34 (H1N1) strain with high selectivity, and one derivative also showed promising activity against the highly pathogenic A(H7N9) strain. A representative compound demonstrated high metabolic stability in murine blood in vitro and exhibited promising pharmacokinetic properties in vivo following intragastric administration in mice. Mechanistic studies revealed two distinct profiles: one subset of inhibitors likely targets viral entry, while another appears to interfere with a later stage, such as assembly; their action is not mediated by neuraminidase inhibition. These findings establish monoterpenoid benzamides bearing the bicyclo[2.2.1]heptane motif as a promising scaffold for the development of anti-influenza agents, warranting further investigation into their precise molecular target and in vivo efficacy.
KW - Antiviral agents
KW - Influenza a virus
KW - Monoterpenoids
KW - Structure-activity relationship
KW - Вирус гриппа А
KW - Противовирусные средства
KW - Монотерпеноиды
KW - Взаимосвязь «структура — активность»
UR - https://www.mendeley.com/catalogue/1da03eb9-f38c-3678-8a3f-6d27d9686d50/
UR - https://www.scopus.com/pages/publications/105030211732
UR - https://www.elibrary.ru/item.asp?id=89829494
U2 - 10.1016/j.bmc.2026.118555
DO - 10.1016/j.bmc.2026.118555
M3 - Article
C2 - 41539082
VL - 135
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
M1 - 118555
ER -
ID: 85172006