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Bicyclic monoterpenoid-based orthopoxvirus inhibitors : Design, synthesis, and biological assessment of a novel amide series. / Tishchenko, Serafim A.; Sokolova, Anastasiya S.; Samsonova, Valeriya V. и др.

в: RSC Medicinal Chemistry, Том 17, № 5, 09.04.2026, стр. 2605-2629.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

Harvard

Tishchenko, SA, Sokolova, AS, Samsonova, VV, Pushkareva, JG, Bormotov, NI, Moskalev, IA, Solomina, DE, Rogachev, AD, Fatyanova, AV, Borisevich, SS, Yarovaya, OI, Serova, OA, Ovchinnikova, AS, Sergeev, AA, Shishkina, LN, Sergeev, AA, Agafonov, AP & Salakhutdinov, NF 2026, 'Bicyclic monoterpenoid-based orthopoxvirus inhibitors: Design, synthesis, and biological assessment of a novel amide series', RSC Medicinal Chemistry, Том. 17, № 5, стр. 2605-2629. https://doi.org/10.1039/d6md00217j

APA

Tishchenko, S. A., Sokolova, A. S., Samsonova, V. V., Pushkareva, J. G., Bormotov, N. I., Moskalev, I. A., Solomina, D. E., Rogachev, A. D., Fatyanova, A. V., Borisevich, S. S., Yarovaya, O. I., Serova, O. A., Ovchinnikova, A. S., Sergeev, A. A., Shishkina, L. N., Sergeev, A. A., Agafonov, A. P., & Salakhutdinov, N. F. (2026). Bicyclic monoterpenoid-based orthopoxvirus inhibitors: Design, synthesis, and biological assessment of a novel amide series. RSC Medicinal Chemistry, 17(5), 2605-2629. https://doi.org/10.1039/d6md00217j

Vancouver

Tishchenko SA, Sokolova AS, Samsonova VV, Pushkareva JG, Bormotov NI, Moskalev IA и др. Bicyclic monoterpenoid-based orthopoxvirus inhibitors: Design, synthesis, and biological assessment of a novel amide series. RSC Medicinal Chemistry. 2026 апр. 9;17(5):2605-2629. doi: 10.1039/d6md00217j

Author

Tishchenko, Serafim A. ; Sokolova, Anastasiya S. ; Samsonova, Valeriya V. и др. / Bicyclic monoterpenoid-based orthopoxvirus inhibitors : Design, synthesis, and biological assessment of a novel amide series. в: RSC Medicinal Chemistry. 2026 ; Том 17, № 5. стр. 2605-2629.

BibTeX

@article{f0c58c65021a471eba9ce1043f7ec11a,
title = "Bicyclic monoterpenoid-based orthopoxvirus inhibitors: Design, synthesis, and biological assessment of a novel amide series",
abstract = "This study reports the design, synthesis, and comprehensive biological evaluation of a new class of orthopoxvirus inhibitors utilizing natural bicyclic monoterpenoid scaffolds as strategic replacements for synthetic polycyclic cores. A focused library of amides based on camphor, apo-/isocamphane, and nopol-derived amines was synthesized and screened for activity against vaccinia (VACV), cowpox (CPXV), ectromelia (ECTV) and variola (VARV) viruses. Structure–activity relationship (SAR) analysis identified the importance of a para-substituted electron-withdrawing group on the benzamide moiety, with the apocamphanyl amine series yielding the most potent candidate, compound 13d. Compound 13d exhibited potent in vitro antiviral activity with IC50 values of 0.32 μM (VACV), 4.43 μM (CPXV), 3.28 μM (ECTV), and 1.6 μM (VARV) coupled with high selectivity indices (up to 1226). Further profiling revealed metabolic stability of 13d in mouse blood and favorable pharmacokinetics in mice following a single intragastric dose (100 mg kg−1), characterized by rapid absorption and a long elimination half-life (T1/2 ∼ 6.7 h), supportive of once-daily dosing. Computational studies involving pharmacophore analysis, molecular docking, and MD simulations elucidated the binding mode to the p37 phospholipase domain and rationalized the observed SAR, highlighting the critical role of hydrophobic interactions and stereochemistry. These findings validate the bicyclic monoterpenoid platform as a promising strategy for discovering potent, metabolically stable anti-orthopoxvirus agents and establish 13d as a compelling lead candidate for further preclinical development.",
author = "Tishchenko, {Serafim A.} and Sokolova, {Anastasiya S.} and Samsonova, {Valeriya V.} and Pushkareva, {Julia G.} and Bormotov, {Nikolay I.} and Moskalev, {Ivan A.} and Solomina, {Daria E.} and Rogachev, {Artem D.} and Fatyanova, {Alina V.} and Borisevich, {Sophia S.} and Yarovaya, {Olga I.} and Serova, {Olga A.} and Ovchinnikova, {Alena S.} and Sergeev, {Alexander A.} and Shishkina, {Larisa N.} and Sergeev, {Artemiy A.} and Agafonov, {Alexander P.} and Salakhutdinov, {Nariman F.}",
note = "Bicyclic monoterpenoid-based orthopoxvirus inhibitors: design, synthesis, and biological assessment of a novel amide series / S. A. Tishchenko, A. S. Sokolova, V. V. Samsonova [et al.] // RSC Medicinal Chemistry. – 2026. – DOI 10.1039/d6md00217j. – EDN CIQDLK. Funding Group: Funder(s): Russian Science Foundation, Award Id(s): 24-73-00137; Funder(s): Ministry of Science and Higher Education of the Russian Federation, Award Id(s): FWUR-2024-0040",
year = "2026",
month = apr,
day = "9",
doi = "10.1039/d6md00217j",
language = "English",
volume = "17",
pages = "2605--2629",
journal = "RSC Medicinal Chemistry",
issn = "2632-8682",
publisher = "Royal Society of Chemistry",
number = "5",

}

RIS

TY - JOUR

T1 - Bicyclic monoterpenoid-based orthopoxvirus inhibitors

T2 - Design, synthesis, and biological assessment of a novel amide series

AU - Tishchenko, Serafim A.

AU - Sokolova, Anastasiya S.

AU - Samsonova, Valeriya V.

AU - Pushkareva, Julia G.

AU - Bormotov, Nikolay I.

AU - Moskalev, Ivan A.

AU - Solomina, Daria E.

AU - Rogachev, Artem D.

AU - Fatyanova, Alina V.

AU - Borisevich, Sophia S.

AU - Yarovaya, Olga I.

AU - Serova, Olga A.

AU - Ovchinnikova, Alena S.

AU - Sergeev, Alexander A.

AU - Shishkina, Larisa N.

AU - Sergeev, Artemiy A.

AU - Agafonov, Alexander P.

AU - Salakhutdinov, Nariman F.

N1 - Bicyclic monoterpenoid-based orthopoxvirus inhibitors: design, synthesis, and biological assessment of a novel amide series / S. A. Tishchenko, A. S. Sokolova, V. V. Samsonova [et al.] // RSC Medicinal Chemistry. – 2026. – DOI 10.1039/d6md00217j. – EDN CIQDLK. Funding Group: Funder(s): Russian Science Foundation, Award Id(s): 24-73-00137; Funder(s): Ministry of Science and Higher Education of the Russian Federation, Award Id(s): FWUR-2024-0040

PY - 2026/4/9

Y1 - 2026/4/9

N2 - This study reports the design, synthesis, and comprehensive biological evaluation of a new class of orthopoxvirus inhibitors utilizing natural bicyclic monoterpenoid scaffolds as strategic replacements for synthetic polycyclic cores. A focused library of amides based on camphor, apo-/isocamphane, and nopol-derived amines was synthesized and screened for activity against vaccinia (VACV), cowpox (CPXV), ectromelia (ECTV) and variola (VARV) viruses. Structure–activity relationship (SAR) analysis identified the importance of a para-substituted electron-withdrawing group on the benzamide moiety, with the apocamphanyl amine series yielding the most potent candidate, compound 13d. Compound 13d exhibited potent in vitro antiviral activity with IC50 values of 0.32 μM (VACV), 4.43 μM (CPXV), 3.28 μM (ECTV), and 1.6 μM (VARV) coupled with high selectivity indices (up to 1226). Further profiling revealed metabolic stability of 13d in mouse blood and favorable pharmacokinetics in mice following a single intragastric dose (100 mg kg−1), characterized by rapid absorption and a long elimination half-life (T1/2 ∼ 6.7 h), supportive of once-daily dosing. Computational studies involving pharmacophore analysis, molecular docking, and MD simulations elucidated the binding mode to the p37 phospholipase domain and rationalized the observed SAR, highlighting the critical role of hydrophobic interactions and stereochemistry. These findings validate the bicyclic monoterpenoid platform as a promising strategy for discovering potent, metabolically stable anti-orthopoxvirus agents and establish 13d as a compelling lead candidate for further preclinical development.

AB - This study reports the design, synthesis, and comprehensive biological evaluation of a new class of orthopoxvirus inhibitors utilizing natural bicyclic monoterpenoid scaffolds as strategic replacements for synthetic polycyclic cores. A focused library of amides based on camphor, apo-/isocamphane, and nopol-derived amines was synthesized and screened for activity against vaccinia (VACV), cowpox (CPXV), ectromelia (ECTV) and variola (VARV) viruses. Structure–activity relationship (SAR) analysis identified the importance of a para-substituted electron-withdrawing group on the benzamide moiety, with the apocamphanyl amine series yielding the most potent candidate, compound 13d. Compound 13d exhibited potent in vitro antiviral activity with IC50 values of 0.32 μM (VACV), 4.43 μM (CPXV), 3.28 μM (ECTV), and 1.6 μM (VARV) coupled with high selectivity indices (up to 1226). Further profiling revealed metabolic stability of 13d in mouse blood and favorable pharmacokinetics in mice following a single intragastric dose (100 mg kg−1), characterized by rapid absorption and a long elimination half-life (T1/2 ∼ 6.7 h), supportive of once-daily dosing. Computational studies involving pharmacophore analysis, molecular docking, and MD simulations elucidated the binding mode to the p37 phospholipase domain and rationalized the observed SAR, highlighting the critical role of hydrophobic interactions and stereochemistry. These findings validate the bicyclic monoterpenoid platform as a promising strategy for discovering potent, metabolically stable anti-orthopoxvirus agents and establish 13d as a compelling lead candidate for further preclinical development.

UR - https://www.mendeley.com/catalogue/178da9b7-345b-3a81-9d86-c1115864b5be/

UR - https://www.scopus.com/pages/publications/105036407049

UR - https://elibrary.ru/item.asp?id=90935817

U2 - 10.1039/d6md00217j

DO - 10.1039/d6md00217j

M3 - Article

VL - 17

SP - 2605

EP - 2629

JO - RSC Medicinal Chemistry

JF - RSC Medicinal Chemistry

SN - 2632-8682

IS - 5

ER -

ID: 83093454