5-Acetyl-2-arylbenzimidazoles as antiviral agents. Part 4

Within a project aimed at discovering new Flaviviridae inhibitors, new variously substituted 2-phenylbenzimidazoles were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representatives of the three genera of the Flaviviridae family, i.e.: Pestivirus (BVDV), Flavivirus (YFV) and Hepacivirus (HCV). Title compounds were also tested against RNA viruses representative of other single-stranded, positive-sense (ssRNA+) negative-sense (RNA−), or double-stranded (dsRNA) genomes, as well as against representatives of two DNA virus families.Nine compounds showed activity against BVDV (EC50 = 0.8–8.0 μM), compound 31 being the most potent (EC50 = 0.80 μM) and selective (SI = CC50/EC50 = >100). When tested in an HCV replicon assay, compound 31 resulted again the most potent, displaying an EC50 value of 1.11 μM and an SI of 100. Besides inhibiting BVDV, two compounds (35 and 38) showed a moderate activity also against YFV (EC50 = 13 μM). Interestingly, 35 was moderately active also against RSV (EC50 = 25 μM).

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► We prepared fifty 5-acetyl-2-arylbenzimidazoles endowed with antiviral activities.
► Nine of these showed to be potently active against BVDV.
► One thiosemicarbazone (compound 31) was active in an HCV replicon assay.
► Some derivatives were active against yellow fever, respiratory syncytial, coxsackie viruses.