Synthesis and In Vitro Evaluation of the Anti-Viral Activity of N-[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkylcarboxamides

Antonio      Carta; Giovanni      Loriga; Sandra      Piras; Giuseppe      Paglietti; Marco      Ferrone; Maurizio      Fermeglia; Sabrina      Pricl; Paolo      La Colla; Barbara      Secci; Gabriella      Collu; Roberta      Loddo

Abstract

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 M; EC50 = 10μ M) and 9l, which was the most active against Sb-1 (CC50 90μM; EC50 = 30μm). 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).

Keywords: Benzotriazolylphenylcarboxamides, Anti-viral activity, Picornaviridae, Cytotoxicity, SAR, Polio virus (Sb-1)helicase, in silico evaluation

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