Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives.
Twelve aminoarylazocompounds (A-C) and 46 aryltriazene 7 derivatives (D-G) have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. Eight aminoazocompounds and 27 aryltriazene derivatives exhibited antiviral activity, sometimes of high level, against one or more viruses. A marked activity against BVDV and YFV was prevailing among the former compounds, while the latter type of compounds affected mainly CVB-2 and RSV. None of the active compounds inhibited the multiplication of HIV-1, VSV and VV. Arranged in order of decreasing potency and selectivity versus the host cell lines, the best compounds are the following; BVDV: 1>7>8>4; YFV: 7>5; CVB-2: 25>56>18; RSV: 14>20>55>38>18>19; HSV-1: 2. For these compounds the EC(50) ranged from 1.6 microM (1) to 12 microM (18), and the S. I. from 19.4 (1) to 4.2 (2). Thus the aminoarylazo and aryltriazene substructures appear as interesting molecular component for developing antiviral agents against ss RNA viruses, particularly against RSV and BVDV, which are important human and veterinary pathogens. Finally, molecular modeling investigations indicated that compounds of structure A-C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC(50) and the experimental EC(50) values.
Tonelli
Michele
M
Dipartimento di Scienze Farmaceutiche, Università di Genova, Genova, Italy.
Vazzana
Iana
I
Tasso
Bruno
B
Boido
Vito
V
Sparatore
Fabio
F
Fermeglia
Maurizio
M
Paneni
Maria Silvia
MS
Posocco
Paola
P
Pricl
Sabrina
S
La Colla
Paolo
P
Ibba
Cristina
C
Secci
Barbara
B
Collu
Gabriella
G
Loddo
Roberta
R
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004267:DNA Viruses / Q000187:drug effects*; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012328:RNA Viruses / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000187:drug effects; D013329:Structure-Activity Relationship; D014226:Triazenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism
D000998:Antiviral Agents; D001391:Azo Compounds; D014226:Triazenes; D014758:Viral Core Proteins; D012324:RNA-Dependent RNA Polymerase