Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses; European Journal of Medicinal Chemistry; Vol. 300
| Parent link: | European Journal of Medicinal Chemistry.— .— Amsterdam: Elsevier Science Publishing Company Inc. Vol. 300.— 2025.— Article number 118124, 16 p. |
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| Outros Autores: | , , , , , , , , , , , , , , , , , , , |
| Resumo: | Title screen The study presents the discovery of a novel class of N-arylated 1,2,4-oxadiazol-5(4H)-ones as potent inhibitors of orthopoxviruses, including the variola virus (VARV). Through systematic structural modifications, two lead compounds, 4 (4-CF3/4-NO2) and 10 (4-I/4-NO2), demonstrated in submicromolar concentration antiviral activity against Vaccinia virus (VACV), cowpox virus (CPXV), ectromelia virus (ECTV), and VARV, with selectivity indices (SI) up to 13738. Studies of mechanisms of action, including time-of-addition experiments and molecular modeling, have shown that these compounds can target the conserved protein p37, which plays a key role in the envelope of the virus. Furthermore, bioinformatic analysis revealed potential interactions with late-stage replication proteins encoded by the A39R and C8L genes. The synthesized derivatives showed activity higher than that of Cidofovir, although they were less effective than that of Tecovirimate. This work highlights the potential of oxadiazolone-based scaffolds as broad-spectrum antipoxviral agents that meet the unmet need for therapy against emerging and re-emerging orthopoxviral threats Текстовый файл AM_Agreement |
| Idioma: | inglês |
| Publicado em: |
2025
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| Assuntos: | |
| Acesso em linha: | https://doi.org/10.1016/j.ejmech.2025.118124 |
| Formato: | Recurso Eletrônico Capítulo de Livro |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=686522 |
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| 200 | 1 | |a Expanding the antiviral arsenal: N-arylated 1,2,4-oxadiazol-5(4H)-ones show high activity against orthopoxviruses |f Artem V. Semenov, Sergey V. Baykov, Natalia S. Soldatova [et al.] | |
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| 300 | |a Title screen | ||
| 320 | |a References: 47 tit | ||
| 330 | |a The study presents the discovery of a novel class of N-arylated 1,2,4-oxadiazol-5(4H)-ones as potent inhibitors of orthopoxviruses, including the variola virus (VARV). Through systematic structural modifications, two lead compounds, 4 (4-CF3/4-NO2) and 10 (4-I/4-NO2), demonstrated in submicromolar concentration antiviral activity against Vaccinia virus (VACV), cowpox virus (CPXV), ectromelia virus (ECTV), and VARV, with selectivity indices (SI) up to 13738. Studies of mechanisms of action, including time-of-addition experiments and molecular modeling, have shown that these compounds can target the conserved protein p37, which plays a key role in the envelope of the virus. Furthermore, bioinformatic analysis revealed potential interactions with late-stage replication proteins encoded by the A39R and C8L genes. The synthesized derivatives showed activity higher than that of Cidofovir, although they were less effective than that of Tecovirimate. This work highlights the potential of oxadiazolone-based scaffolds as broad-spectrum antipoxviral agents that meet the unmet need for therapy against emerging and re-emerging orthopoxviral threats | ||
| 336 | |a Текстовый файл | ||
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| 461 | 1 | |t European Journal of Medicinal Chemistry |c Amsterdam |n Elsevier Science Publishing Company Inc. | |
| 463 | 1 | |t Vol. 300 |v Article number 118124, 16 p. |d 2025 | |
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a N-Aryl-oxadiazol-5(4H)-Ones | |
| 610 | 1 | |a Orthopoxviruses | |
| 610 | 1 | |a Vaccinia virus | |
| 610 | 1 | |a Cowpox virus | |
| 610 | 1 | |a Mousepox virus | |
| 610 | 1 | |a Variola virus | |
| 610 | 1 | |a Antiviral activity | |
| 610 | 1 | |a Molecular modeling | |
| 610 | 1 | |a Bioinformatics | |
| 701 | 1 | |a Semenov |b A. V. |g Artem Valerjevich |f 1997- |c Chemist |c Research Engineer of Tomsk Polytechnic University |9 89056 | |
| 701 | 1 | |a Baykov |b S. V. |c chemist |c Researcher at Tomsk Polytechnic University, Candidate of Chemical Sciences |f 1987- |g Sergey Valentinovich |9 22856 | |
| 701 | 1 | |a Soldatova |b N. S. |c organic chemist |c engineer of Tomsk Polytechnic University |f 1992- |g Nataliya Sergeevna |9 19363 | |
| 701 | 1 | |a Geyl |b K. K. |g Kirill Konstantinovich | |
| 701 | 1 | |a Shetnev |b A. A. | |
| 701 | 1 | |a Boyarskiy |b V. P. | |
| 701 | 1 | |a Yusubov |b M. S. |c chemist |c Professor of Tomsk Polytechnic University, Doctor of chemical sciences |f 1961- |g Mekhman Suleiman-Ogly (Suleimanovich) |9 15928 | |
| 701 | 1 | |a Bormotov |b N. I. | |
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| 701 | 1 | |a Yarovaya |b O. I. |g Olga Ivanovna | |
| 701 | 1 | |a Salakhutdinov |b N. F. | |
| 701 | 1 | |a Postnikov |b P. S. |c organic chemist |c Associate Professor of Tomsk Polytechnic University, Candidate of chemical sciences |f 1984- |g Pavel Sergeevich |9 15465 | |
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