title: 2-Arylbenzimidazoles as antiviral and antiproliferative agents--Part 2.
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) (EC(50) = 0.5 microM) and CVB-2 at 1 microM 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 microM) 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.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, University of Sassari, Via Muroni, 23-07100 Sassari, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Vitale
authors.forename: Paola
authors.initials: P
authors.lastname: Corona
authors.forename: Mario
authors.initials: M
authors.lastname: Loriga
authors.forename: Antonio
authors.initials: A
authors.lastname: Carta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglietti
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Busonera
authors.forename: Esther
authors.initials: E
authors.lastname: Marongiu
authors.forename: David
authors.initials: D
authors.lastname: Collu
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018067:Flaviviridae / Q000187:drug effects; D006801:Humans
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; C031000:benzimidazole