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

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

Dades bibliogràfiques
Parent link:	European Journal of Medicinal Chemistry.— .— Amsterdam: Elsevier Science Publishing Company Inc. Vol. 300.— 2025.— Article number 118124, 16 p.
Altres autors:	Semenov A. V. Artem Valerjevich, Baykov S. V. Sergey Valentinovich, Soldatova N. S. Nataliya Sergeevna, Geyl K. K. Kirill Konstantinovich, Shetnev A. A., Boyarskiy V. P., Yusubov M. S. Mekhman Suleiman-Ogly (Suleimanovich), Bormotov N. I., Serova O. A., Shishkina L. N., Ovchinnikova A. S., Odnoshevsky D. A., Pjyankov O. V., Borisevich S. S., Gorokhov Ya. V., Nikitin V. N. Vladimir Nikolaevich, Shcherbakov D. N., Yarovaya O. I. Olga Ivanovna, Salakhutdinov N. F., Postnikov P. S. Pavel Sergeevich
Sumari:	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:	anglès
Publicat:	2025
Matèries:	электронный ресурс труды учёных ТПУ N-Aryl-oxadiazol-5(4H)-Ones Orthopoxviruses Vaccinia virus Cowpox virus Mousepox virus Variola virus Antiviral activity Molecular modeling Bioinformatics
Accés en línia:	https://doi.org/10.1016/j.ejmech.2025.118124
Format:	Electrònic Capítol de llibre
KOHA link:	https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=686522

Internet

https://doi.org/10.1016/j.ejmech.2025.118124