Antiviral activity of benzimidazole derivatives. I. Antiviral activity of 1-substituted-2-[(benzotriazol-1/2-yl)methyl]benzimidazoles.
Forty-three 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles, bearing either linear (dialkylamino)alkyl- or bulkier (quinolizidin-1-yl)alkyl moieties at position 1, were evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representative of two of the three genera of the Flaviviridae family, i.e. Flaviviruses (Yellow Fever Virus (YFV)) and Pestiviruses (Bovine Viral Diarrhoea Virus (BVDV)), as Hepaciviruses can hardly be used in routine cell-based assays. Compounds were also tested against representatives of other virus families. Among ssRNA+ viruses were a retrovirus (Human Immunodeficiency Virus type 1 (HIV-1)), two picornaviruses (Coxsackie Virus type B2 (CVB2), and Poliovirus type-1, Sabin strain (Sb-1)); among ssRNA- viruses were a Paramyxoviridae (Respiratory Syncytial Virus (RSV)) and a Rhabdoviridae (Vesicular Stomatitis Virus (VSV)) representative. Among double-stranded RNA (dsRNA) viruses was a Reoviridae representative (Reo-1). Two representatives of DNA virus families were also included: Herpes Simplex type 1, (HSV-1; Herpesviridae) and Vaccinia Virus (VV; Poxviridae). Most compounds exhibited potent activity against RSV, with EC(50) values as low as 20 nM. Moreover, some compounds, in particular when bearing a (quinolizidin-1-yl)alkyl residue, were also moderately active against BVDV, YFV, and CVB2.
Tonelli
Michele
M
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova.
Paglietti
Giuseppe
G
Boido
Vito
V
Sparatore
Fabio
F
Marongiu
Fabio
F
Marongiu
Esther
E
La Colla
Paolo
P
Loddo
Roberta
R
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D004267:DNA Viruses / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005416:Flavivirus / Q000187:drug effects; D000882:Haplorhini; D006801:Humans; D010576:Pestivirus / Q000187:drug effects; D012328:RNA Viruses / Q000187:drug effects; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001562:Benzimidazoles