New Benzimidazole 3′-Deoxynucleosides: Synthesis and Antiherpes Virus Properties

A series of new 3′-deoxyribosides of substituted benzimidazoles was obtained by the chemo-enzymatic method using genetically engineered <i>E. coli </i>purine nucleoside phosphorylase (PNP). In the case of asymmetrically substituted benzimidazole derivatives, a mixture of N1- and N3-regio...

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Main Authors: Aleksandra O. Arnautova, Irina A. Aleksakhina, Ekaterina A. Zorina, Maria Ya. Berzina, Ilya V. Fateev, Barbara Z. Eletskaya, Konstantin V. Antonov, Olga S. Smirnova, Alexander S. Paramonov, Alexey L. Kayushin, Valeria L. Andronova, Georgii A. Galegov, Maria A. Kostromina, Evgeny A. Zayats, Inna L. Karpenko, Svetlana K. Kotovskaya, Valery N. Charushin, Roman S. Esipov, Anatoly I. Miroshnikov, Irina D. Konstantinova
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/7/922
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Summary:A series of new 3′-deoxyribosides of substituted benzimidazoles was obtained by the chemo-enzymatic method using genetically engineered <i>E. coli </i>purine nucleoside phosphorylase (PNP). In the case of asymmetrically substituted benzimidazole derivatives, a mixture of N1- and N3-regioisomers was formed (confirmed by NMR). The antiviral activity of the obtained compounds against herpes simplex virus 1 of reference strain L2 and a strain deeply resistant to acyclovir in Vero E6 cell culture was studied. 4,6-Difluoro-1-(β-D-3′-deoxyribofuranosyl)benzimidazole (IC<sub>50</sub> = 250.92 µM, SI = 12.00) and 4,5,6-trifluoro-1-(β-D-3′-deoxyribofuranosyl)benzimidazole (IC<sub>50</sub> = 249.96 µM, SI = 16.00) showed significant selective activity against both viral models in comparison to ribavirin (IC<sub>50</sub> = 511.88 µM, SI > 8.00).
ISSN:2218-273X