Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives.
Seventy-six 2-phenylbenzimidazole derivatives were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, BVDV, Sb-1, HSV-1, and YFV, while HIV-1 and VSV were not affected, and RSV, VV and Reo-1 were only susceptible to a few compounds. Thirty-nine compounds exhibited high activity (EC(50)=0.1-10microM) against at least one virus, and four of them were outstanding for their high and selective activity against VV (24, EC(50)=0.1microM) and BVDV (50, 51, and 53 with EC(50)=1.5, 0.8, and 1.0microM, respectively). The last compounds inhibited at low micromolar concentrations the NS5B RdRp of BVDV and also of HCV, the latter sharing structural similarity with the former. The considered compounds represent attractive leads for the development of antiviral agents against poxviruses, pestiviruses and even HCV, which are important human and veterinary pathogens.
Tonelli
Michele
M
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy. michele.tonelli@unige.it
Simone
Matteo
M
Tasso
Bruno
B
Novelli
Federica
F
Boido
Vito
V
Sparatore
Fabio
F
Paglietti
Giuseppe
G
Pricl
Sabrina
S
Giliberti
Gabriele
G
Blois
Sylvain
S
Ibba
Cristina
C
Sanna
Giuseppina
G
Loddo
Roberta
R
La Colla
Paolo
P
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004267:DNA Viruses / Q000187:drug effects; D006801:Humans; D012328:RNA Viruses / Q000187:drug effects; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000998:Antiviral Agents; D001562:Benzimidazoles; D054852:Small Molecule Libraries; C117755:2-phenylbenzimidazole