Synthesis, Characterization, Cytotoxicity Analysis and Anti-Dengue Activity of Newer Nucleoside Analogues

Abstract

World Health Organization (WHO) report suggests that dengue the life-threatening disease currently has no specific medication. Hence, present study was intended to synthesize some new nucleoside analogues (NNAs) to combat the dengue virus (DENV-2). Study involved synthesis of 1-(4-((substituted cyclohexyl)methyl)-2-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-3,5-dihydroxy-1,2,4- triazinan-1-yl)ethanone (3a-f) by hydrogenation and acetylation of 4-((substituted-cyclohexa-2,5- dienylidene)methyl)-2-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1,2,4-triazine- 3,5(2H,4H)-dione (3a-f), that was synthesized by treating uridine derivative (1) with various substituted aldehydes. The structures of newly synthesized NNAs were characterized using NMR, FTIR and mass spectrometric data. Effectiveness of the synthesized NNAs against dengue was also evaluated based on their anti-dengue activity using DENV-2 serotype and cytotoxicity evaluation against Vero cells using MTT assay. Present study reports successful synthesis of NNAs 3a-f with high inhibition potential against DENV-2 and minimal to absence of cytotoxicity. Significant anti-dengue activity and least/no cytotoxicity of NNAs against DENV-2 supports their potential application in dengue treatment. However, synthesized NNAs should be further evaluated for preclinical and clinical significance.