ENZYMATIC SYNTHESIS AND ANTIHERPETIC ACTIVITY OF ALKYL-SUBSTITUTED 5-PHENYL-1,2,4-TRIAZOLE-3-THIONE DEOXYRIBOSIDES
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 deoxyribosides of 1,2,4-triazole-3-thione derivatives and test their antiviral activity against herpes simplex virus. Previously synthesized 5-phenyl-1,2,4-triazole-3-thione was reacted with alkyl iodide or alkyl bromide in the presence of potassium carbonate in dry acetone. In this way, methyl, ethyl, propyl, and butyl derivatives were synthesized. All the compounds were substrates for E. coli purine nucleoside phosphorylase (PNP), so enzymatic synthesis of their deoxyribosides was performed. The antiherpetic activity of the synthesized bases and nucleosides was investigated. Both cytotoxicity towards Vero E6 cells and antiviral activity increase with increasing length of the substituent at position 3 in 1,2,4-triazole. The octanol/water partition coefficient (logP), which is a characteristic of lipophilicity, was calculated for the substances tested for antiviral activity. For both heterocyclic bases and nucleosides, an increase in lipophilicity generally leads to an increase in both toxicity and antiviral activity. For all nucleosides, a linear decrease in the CC50 value is observed with increasing LogP. Additionally, for all nucleosides, a linear decrease in the IC50 value is observed with increasing LogP.
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