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

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 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).

Activity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants

“…Compounds (1-6) were evaluated in cell-based assays against the above listed ssRNA þ , dsRNA and ssRNA À viruses, as previously described [1][2][3][4]. Cytotoxicity of compounds was evaluated in parallel with the antiviral activity.…”

Molecular targets for flavivirus drug discovery

“…Several compounds have been identified as RNA helicase of inhibitors of flavi- and other RNA viruses (Borowski et al, 2007; Carta et al, 2006; Frick, 2007; Johansson et al, 2003; Maga et al, 2005; Wu et al, 2006; Xi, 2007). Borowski et al, (2002) reported a WNV helicase inhibitor which also was active in cellular assays (IC 50 = 25–30 μM).…”

Chemistry, Biological Properties and SAR Analysis of Quinoxalinones

“…10 respectively) and investigated whether they were able to potentiate the antiproliferative activity of doxorubicin (Doxo), vincristine (VCR) and etoposide (VP16) in human tumor derived cell lines carrying the Pgp (Doxo and VCR), or MRP (VP16) phenotype [32].…”