Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents

  • Bioorg Med Chem. 2014 Sep 1;22(17):4893-909. doi: 10.1016/j.bmc.2014.06.043.
Michele Tonelli  1 ,  Federica Novelli  2 ,  Bruno Tasso  2 ,  Iana Vazzana  2 ,  Anna Sparatore  3 ,  Vito Boido  2 ,  Fabio Sparatore  2 ,  Paolo La Colla  4 ,  Giuseppina Sanna  4 ,  Gabriele Giliberti  4 ,  Bernardetta Busonera  4 ,  Pamela Farci  4 ,  Cristina Ibba  4 ,  Roberta Loddo  5
Affiliations
  • 1. Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy. Electronic address: [email protected].
  • 2. Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
  • 3. Dipartimento di Scienze Farmaceutiche, Università di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
  • 4. Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
  • 5. Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy. Electronic address: [email protected].
PMID: 25082514 DOI: 10.1016/j.bmc.2014.06.043
Abstract

A library of eighty-six assorted benzimidazole derivatives was screened for Antiviral activity against a panel of ten RNA and DNA viruses. Fifty-two of them displayed different levels of activity against one or more viruses, among which CVB-5, RSV, BVDV and Sb-1 were the most frequently affected. In particular, fourteen compounds exhibited an EC50 in the range 9-17μM (SI from 6 to >11) versus CVB-5, and seven compounds showed an EC50 in the range 5-15μM (SI from 6.7 to ⩾20) against RSV, thus resulting comparable to or more potent than the respective reference drugs (NM108 and ribavirin). Most of these compounds derive from 2-benzylbenzimidazole, but also Other molecular scaffolds [as 1-phenylbenzimidazole (2), 2-trifluoromethylbenzimidazole (69), dihydropyrido[3',2':4,5]imidazo[1,2-a][1,4]benzodiazepin-5-one (3), dibenzo[c,e]benzimidazo[1,2-a]azepine (22), and 2-(tetrahydropyran-2-yl)benzimidazole (81, 82 and 86)] are related to interesting levels of activity against these or Other viruses (BVDV, Sb-1). Thus, these scaffolds (some of which, so far unexplored), represent valid starting points to develop more efficient agents against pathologies caused by CVB-5, RSV, BVDV and Sb-1 viruses.

Keywords
Anti-CVB-5; Benzimidazole derivatives; RNA and DNA viruses; anti-RSV, anti-Sb-1 activity.