Design, Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents

• Published in: International journal of molecular sciences Vol. 23; no. 11; p. 6307
• Main Authors: Zhang, Chao, Tang, Yun-Sang, Meng, Chu-Ren, Xu, Jing, Zhang, De-Liang, Wang, Jian, Huang, Er-Fang, Shaw, Pang-Chui, Hu, Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.06.2022; MDPI
• Subjects: Acids; Avian flu; Cytotoxicity; Drug resistance; Genomes; Hydrocarbons; Pharmaceutical industry; Proteins; RNA polymerase; Viral infections; Viruses; 4-[(quinolin-4-yl)amino]benzamide derivatives; pharmacophore; RNA-dependent RNA polymerase; anti-influenza virus; molecular dynamics simulation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23116307

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.