Flavonol Derivatives Containing a Quinazolinone Moiety: Design, Synthesis, and Antiviral Activity

• Published in: Chemistry & biodiversity 2024-02, Vol.21 (2), p.e202301737-n/a
• Main Authors: Gong, Chenyu, Meng, Kaini, Sun, Zhiling, Zeng, Wei, An, Youshan, Zou, Hongqian, Qiu, Yujiao, Liu, Da, Xue, Wei
• Format: Article
• Language: English
• Subjects: Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; Antiviral drugs; Coat protein; Disease resistance; Drug Design; Flavonol derivatives; Flavonols; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Quinazolinone; Quinazolinones; Quinazolinones - pharmacology; Structure-Activity Relationship; Thermophoresis; TMV-CP; Tobacco; Tobacco Mosaic Virus
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202301737

A series of flavonol derivatives containing quinazolinone were designed and synthesized, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results of the half maximal effective concentration (EC50) test against TMV showed that the EC50 value of curative activity of K5 was 139.6 μg/mL, which was better than that of the commercial drug ningnanmycin (NNM) 296.0 μg/mL, and the EC50 value of protective activity of K5 was 120.6 μg/mL, which was superior to that of NNM 207.0 μg/mL. The interaction of K5 with TMV coat protein (TMV‐CP) was investigated using microscale thermophoresis (MST) and molecular docking and the results showed that K5 can combine with TMV‐CP more strongly to TMV‐CP than that NNM can. Furthermore, the assay measuring malondialdehyde (MDA) content indicated that K5 had the ability to improve the disease resistance of tobacco. Hence, this study offers strong evidence that flavonol derivatives have potential as novel antiviral agents.