Antiviral activity of benzotriazole derivatives. 5-[4-(Benzotriazol-2-yl)phenoxy]-2,2-dimethylpentanoic acids potently and selectively inhibit Coxsackie Virus B5

  • Bioorg Med Chem. 2015 Nov 1;23(21):7024-34. doi: 10.1016/j.bmc.2015.09.035.
Roberta Loddo  1 ,  Federica Novelli  2 ,  Anna Sparatore  3 ,  Bruno Tasso  2 ,  Michele Tonelli  4 ,  Vito Boido  2 ,  Fabio Sparatore  2 ,  Gabriella Collu  5 ,  Ilenia Delogu  5 ,  Gabriele Giliberti  5 ,  Paolo La Colla  5
Affiliations
  • 1. Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy. Electronic address: [email protected].
  • 2. Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
  • 3. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
  • 4. Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy. Electronic address: [email protected].
  • 5. Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
PMID: 26443549 DOI: 10.1016/j.bmc.2015.09.035
Abstract

A library of 64 benzotriazole derivatives (17 of which were [4-(benzotriazol-2-yl)phenoxy]alkanoic acids) were screened for Antiviral activity against a panel of twelve DNA and RNA viruses. Twenty-six compounds (12 of which were [4-(benzotriazol-2-yl)phenoxy]alkanoic acids) displayed activity against one or more viruses. CVB-5, RSV, BVDV, Sb-1 and YFV were, in decreasing order, the more frequently and effectively affected viruses; DENV-2, WNV, HIV-1 and Reo-1 were only occasionally and modestly affected, while the remaining viruses were not affected by any of the tested compounds. Worth of note were compounds 33 and 35; the former for the activity against Sb-1 (EC50=7 μM) and the latter for the large spectrum of activity including six viruses with a mean EC50=12 μM. Even more interesting were the alkanoic acids 45-48 and 50-57 for their activity against RSV and/or CVB-5. In particular, compound 56 displayed a potent and selective activity against CVB-5 with EC50=0.15 μM and SI=100, thus representing a valuable hit compound for the development of Antiviral agents for the treatment of human pathologies related to this virus.

Keywords
Anti-Flaviviridae agents; Antiviral agents; Coxsackie Virus B5 inhibitors; N-Substituted benzotriazoles; RSV inhibitors.