title: Antiviral activity of benzotriazole derivatives. 5-[4-(Benzotriazol-2-yl)phenoxy]-2,2-dimethylpentanoic acids potently and selectively inhibit Coxsackie Virus B5.
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.
authors.affiliation: Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy. Electronic address: rloddo@unica.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tasso
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy. Electronic address: michele.tonelli@unige.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Boido
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sparatore
authors.affiliation: Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Collu
authors.affiliation: Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Delogu
authors.affiliation: Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Giliberti
authors.affiliation: Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004267:DNA Viruses / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D029822:Enterovirus B, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D012328:RNA Viruses / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D014230:Triazoles; C012771:benzotriazole
keywords: Anti-Flaviviridae agents; Antiviral agents; Coxsackie Virus B5 inhibitors; N-Substituted benzotriazoles; RSV inhibitors