2-Arylbenzimidazoles as Antiviral and Antiproliferative Agents-Part 2

Gabriella      Vitale; Paola      Corona; Mario      Loriga; Antonio      Carta; Giuseppe      Paglietti; Paolo   La   Colla; Bernardetta      Busonera; Esther      Marongiu; David      Collu; Roberta      Loddo

doi:10.2174/157340609790170542

Abstract

In prosecution of an anti-Flaviviridae project a new series of variously substituted 2-diphenyl-benzimidazoles were synthesized and tested in vitro for antiviral and antiproliferative activities. Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae). The 5- Acetyl-2-(4-nitrobiphenyl-4-yl)-1H-benzimidazole (24) emerged as potent active lead compound against Yellow Fever Virus (a Flavivirus) (EC50= 0.5 μM) and CVB-2 at 1 μM and was not cytotoxic, whereas the other title benzimidazoles showed no antiviral activity at concentrations not cytotoxic for the resting cell monolayers. Among the examined series, the most cytotoxic derivatives (11,12,14,16,18,19,20,21,23,25-30) against mock-infected MT-4 cells (CC50 < 8.0 μM) were evaluated against a panel of human cell lines derived from haematological and solid tumours, using 6-mercaptopurine (6-MP) and etoposide as reference drugs. In particular, compounds 26 and 28 showed a similar potency of 6-MP and etoposide.

Keywords: 2-Arylbenzimidazoles, Antiviral, antiproliferative activities, Flaviviridae, Retroviridae, Poxviridae

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