Antimicrobial and cytotoxic arylazoenamines. Part III: antiviral activity of selected classes of arylazoenamines.
Eighty-five arylazoenamines, characterized by different types of aryl and basic moieties, have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of ten RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, RSV, BVDV, YFV, and Sb-1; the remaining viruses were either not affected (HIV-1, VSV, and VV) or susceptible only to a very few compounds (Reo-1 and HSV-1). Thirty-five compounds exhibited high activity, with EC(50) in the range 0.8-10 microM, and other 28 compounds had EC(50) between 11 and 30 microM, thus indicating that the arylazoenamine molecular pattern is an interesting novel pharmacophore for antiviral agents against ssRNA viruses. Moreover, some compounds (as 28, 32, 42, and 53) appear of high interest, being devoid of toxicity on the human MT-4 cells (CC(50)>100 microM). A ligand-based computational approach was employed to identify highly predictive pharmacophore models for the most frequently affected viruses CVB-2, RSV, and BVDV. These models should allow the design of second generation of more potent inhibitors of these human and veterinary pathogens.
Tonelli
Michele
M
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV 3, 16132 Genova, Italy.
Boido
Vito
V
Canu
Caterina
C
Sparatore
Anna
A
Sparatore
Fabio
F
Paneni
Maria Silvia
MS
Fermeglia
Maurizio
M
Pricl
Sabrina
S
La Colla
Paolo
P
Casula
Laura
L
Ibba
Cristina
C
Collu
David
D
Loddo
Roberta
R