Design,Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents |
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Authors: | Chao Zhang Yun-Sang Tang Chu-Ren Meng Jing Xu De-Liang Zhang Jian Wang Er-Fang Huang Pang-Chui Shaw Chun Hu |
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Affiliation: | 1.Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; (C.Z.); (C.-R.M.); (J.X.); (D.-L.Z.); (J.W.); (E.-F.H.);2.School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China; |
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Abstract: | In this study, a series of 4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay (EC50 = 11.38 ± 1.89 µM) and plaque inhibition assay (IC50 = 0.23 ± 0.15 µM). G07 also exhibited significant anti-influenza virus activities against other three different influenza virus strains A/PR/8 (H1N1), A/HK/68 (H3N2) and influenza B virus. According to the result of ribonucleoprotein reconstitution assay, G07 could interact well with ribonucleoprotein with an inhibition rate of 80.65% at 100 µM. Furthermore, G07 exhibited significant activity target PA−PB1 subunit of RNA polymerase according to the PA−PB1 inhibitory activity prediction by the best pharmacophore Hypo1. In addition, G07 was well drug-likeness based on the results of Lipinski’s rule and ADMET prediction. All the results proved that 4-[(quinolin-4-yl)amino]benzamide derivatives could generate potential candidates in discovery of anti-influenza virus agents. |
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Keywords: | anti-influenza virus 4-[(quinolin-4-yl)amino]benzamide derivatives molecular dynamics simulation RNA-dependent RNA polymerase pharmacophore |
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