title: Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents.
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.
authors.affiliation: Dipartimento di Farmacia, Università 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 di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tasso
authors.affiliation: Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
authors.forename: Iana
authors.initials: I
authors.lastname: Vazzana
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
authors.affiliation: Dipartimento di Farmacia, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Boido
authors.affiliation: Dipartimento di Farmacia, Università 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 di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sanna
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Giliberti
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Busonera
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Farci
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ibba
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy. Electronic address: rloddo@unica.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004770:Enterovirus / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D017955:Poliovirus / Q000187:drug effects*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; C031000:benzimidazole
keywords: Anti-CVB-5; Benzimidazole derivatives; RNA and DNA viruses; anti-RSV, anti-Sb-1 activity