Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase
Year: 2024
Type: article
Abstract: 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 E. coli 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/RACV) in Vero E6 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-D-ribofuranosyl)-1,2,4-triazole and 5-butylthio-1-(2-deoxy-β-D-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.
Source: Biomolecules
DOI: 10.3390/biom14070745
Authors: Ilya V. Fateev, Sobirdjan A. Sasmakov, Jaloliddin M. Abdurakhmanov, Abdukhakim A. Ziyaev, Shukhrat Sh. Khasanov, Farkhod B. Eshboev, Oybek N. Ashirov, Valeriya D. Frolova, Barbara Z. Eletskaya, Olga S. Smirnova, Maria Ya. Berzina, Alexandra O. Arnautova, Yulia A. Abramchik, Maria A. Kostromina, Alexey L. Kayushin, Konstantin V. Antonov, Alexander S. Paramonov, Valeria L. Andronova, Georgiy A. Galegov, Roman S. Esipov, Shakhnoz S. Azimova, Anatoly I. Miroshnikov, Irina D. Konstantinova
Institutions: Russian Academy of Sciences, Institute of Bioorganic Chemistry, Academy of Sciences Republic of Uzbekistan, Yunusov Institute of the Chemistry of Plant Substances, Gamalei Institute of Epidemiology and Microbiology, D.I. Ivanovsky Institute of Virology Russian Academy of Medical Sciences, Ministry of Health of the Russian Federation
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,069
Funder: Russian Science Foundation
Awards: G5022747290, G6122101025
OpenAlex ID: W4399962829