Natural pyrrolo[1,2-a]quinazolinone derivatives: Design, synthesis, characterization, and bio-evaluation as novel antiviral agents

文献类型： 外文期刊

第一作者： Wei, Yanhong

作者： Wei, Yanhong;Zheng, Fuqiang;Chen, Wenxuan;Li, Ying;Alateng, W.;Su, Jianglong;Kong, Mengmeng;Zheng, Fuqiang;Guo, Lirong;Wang, Hexiang;Bao, Longzhu;Wu, Zhaoyuan;Ke, Shaoyong;Guo, Lirong;Wang, Hexiang

作者机构：

关键词： Natural product; Pyrrolo[1; a ]quinazolinone derivatives; Antiviral agents; EV71; CVB3

期刊名称：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY （ 影响因子：5.9； 五年影响因子：6.4 ）

ISSN： 0223-5234

年卷期： 2025 年 288 卷

页码：

收录情况： SCI

摘要： As viral infectious diseases increasingly threaten global health, antiviral drug research has become a focus in the medicinal chemistry. Enterovirus has always been an important virus causing infections disease with a high incidence in summer and autumn, such as Enterovirus 71 (EV71) and Coxsackievirus B3 (CVB3). Currently, no specific antiviral drugs are available for EV71 and CVB3. So, we designed and synthesized a novel series of quinazolinone derivatives based on the natural pyrrolo[1,2-a]quinazolinone scaffold, which were fully characterized and identified as potential anti-enterovirus agents. Among them, compound B9 exhibited potent antiCVB3 activity with an EC50 value of 17.4 +/- 3.62 mu M, and compound B5 exhibited potent anti-EV71 activity with an EC50 value of 14.8 +/- 2.18 mu M as confirmed by determining the cytopathic effects, progeny virus titers, viral nucleic acid and protein levels. The potential antiviral mechanisms of compound B5 were also explored. The compound B5 exhibited a powerful therapeutic effect primarily by blocking the post-attachment stage of viral infection. Further experiments demonstrated that compound B5 didn't inhibit the activities of the EV71 2Apro and 3Dpol. Modelling of the molecular binding of the 3Cpro-compound complex revealed that the compound B5 could insert into the substrate-binding pocket of EV71 3Cpro, blocking substrate recognition and possibly inhibiting EV71 3Cpro activity. These researches may provide evidence for the development of these novel pyrrolo[1,2-a]quinazolinone derivatives derived from natural products as potential antiviral agents.

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