Synthesis and in vitro evaluation of the anti-viral activity of N-[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkylcarboxamides.
A series N-[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkylcarboxamides (8e-k, 9e-i, k, l) and their parent amines (5a-c and 6a-d) were prepared according to Schemes (1 and 2). Compounds were evaluated in vitro for cytotoxicity and antiviral activity against a wide spectrum of RNA (positive- and negative-sense) viruses, like [Bovine Viral Diarrhea Virus (BVDV), Yellow Fever Virus (YFV), Coxsackie Virus B (CVB-2), Polio Virus (Sb-1), Human Immunodeficiency Virus (HIV-1), Respiratory Syncytial Virus (RSV)] or double-stranded (dsRNA) virus, like Reoviridae (Reo-1). The Entero (CVB-2 and Sb-1) were the only viruses inhibited by title compounds. In particular, two of them emerged for their selective, although not very potent, antiviral activity: 8i, which was the most active against CVB-2 (CC50 >100 microM; EC50 = 10 microM) and 9l, which was the most active against Sb-1 (CC50 90 microM; EC50 = 30 microm). Title compounds were evaluated in silico against the Sb-1 helicase, as the crystal structure of this enzyme was not available, the corresponding 3D model was obtained by homology techniques (see Fig. 2).
Carta
Antonio
A
Dipartimento Farmaco Chimico Tossicologico, Facoltà di Farmacia, Università di Sassari, via Muroni 23/a, 07100 Sassari, Italy. acarta@uniss.it
Loriga
Giovanni
G
Piras
Sandra
S
Paglietti
Giuseppe
G
Ferrone
Marco
M
Fermeglia
Maurizio
M
Pricl
Sabrina
S
La Colla
Paolo
P
Secci
Barbara
B
Collu
Gabriella
G
Loddo
Roberta
R
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D020365:RNA Helicases / Q000037:antagonists & inhibitors; D012328:RNA Viruses / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000577:Amides; D000998:Antiviral Agents; D020365:RNA Helicases