Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase

Fateev, I.V.; Sasmakov, S.A.; Abdurakhmanov, J.M.; Ziyaev, A.A.; Khasanov, S.S.; Eshboev, F.B.; Ashirov, O.N.; Frolova, V.D.; Eletskaya, B.Z.; Smirnova, O.S.; Berzina, M.Y.; Arnautova, A.O.; Abramchik, Y.A.; Kostromina, M.A.; Kayushin, A.L.; Antonov, K.V.; Paramonov, A.S.; Andronova, V.L.; Galegov, G.A.; Esipov, R.S.; Azimova, S.S.; Miroshnikov, A.I.; Konstantinova, I.D.

Авторы: Fateev Ilya V., Sasmakov Sobirdjan A., Abdurakhmanov Jaloliddin M., Ziyaev Abdukhakim A., Khasanov Shukhrat Sh, Eshboev Farkhod B., Ashirov Oybek N., Frolova Valeriya D., Eletskaya Barbara Z., Smirnova Olga S., Berzina Maria Ya, Arnautova Alexandra O., Abramchik Yulia A., Kostromina Maria A., Kayushin Alexey L., Antonov Konstantin V., Paramonov Alexander S., Andronova Valeria L., Galegov Georgiy A., Esipov Roman S., Azimova Shakhnoz S., Miroshnikov Anatoly I., Konstantinova Irina D.
Журнал: Biomolecules
Том: 14
Номер: 7
Год издания: 2024
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 745
Последняя страница: 745
DOI: 10.3390/biom14070745
Аннотация: 1,2,4-Triazole derivatives have a wide range of biological activities. The most well-known drug that contains 1,2,4-triazole as part of its structure is the nucleoside analogue ribavirin, an antiviral drug. Finding new nucleosides based on 1,2,4-triazole is a topical task. The aim of this study was to synthesize ribosides and deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex viruses. Three compounds from a series of synthesized mono- and disubstituted 1,2,4-triazole-3-thione derivatives were found to be substrates for purine nucleoside phosphorylase. Of six prepared nucleosides, the riboside and deoxyriboside of 3-phenacylthio-1,2,4-triazole were obtained at good yields. The yields of the disubstituted 1,2,4-triazol-3-thiones were low due to the effect of bulky substituents at the C3 and C5 positions on the selectivity of enzymatic glycosylation for one particular nitrogen atom in the triazole ring. The results of cytotoxic and antiviral studies on acyclovir-sensitive wild-type strain HSV-1/L2(TK+) and acyclovir-resistant strain (HSV-1/L2/R) in cell culture showed that the incorporation of a thiobutyl substituent into the C5 position of 3-phenyl-1,2,4-triazole results in a significant increase in the cytotoxicity of the base and antiviral activity. The highest antiviral activity was observed in the 3-phenacylthio-1-(β--ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β--ribofuranosyl)-3-phenyl-1,2,4-triazole nucleosides, with their selectivity indexes being significantly higher than that of ribavirin. It was also found that with the increasing lipophilicity of the nucleosides, the activity and toxicity of the tested compounds increased.
Добавил в систему: Есипов Роман Станиславович

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Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylaseстатья