State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, P. R. China.
J Agric Food Chem. 2021 Dec 8;69(48):14459-14466. doi: 10.1021/acs.jafc.1c03555. Epub 2021 Nov 22.
A series of unreported novel dithioacetal derivatives containing a 4(3)-quinazolinone pyrimidine ring were synthesized, and their antiviral activities were evaluated against tomato spotted wilt virus (TSWV). A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was established, and compound was designed and synthesized according to the analysis results of the CoMFA and CoMSIA models. The bioassay results showed that compound exhibited excellent inactivation activity against TSWV, with EC values of 144 g/mL, which was better than those of ningnanmycin (149 g/mL) and the lead compound xiangcaoliusuobingmi (525 g/mL). The binding ability of compound to TSWV CP was tested by microscale thermophoresis (MST), and the binding constant value was 4.4 M, which was better than those of ningnanmycin (6.2 M) and xiangcaoliusuobingmi (59.1 M). Therefore, this study indicates that novel dithioacetal derivatives containing a 4(3)-quinazolinone pyrimidine ring may be applied as new antiviral agents.
一系列未经报道的新型含 4(3)-喹唑啉酮嘧啶环的二硫缩醛衍生物被合成，并对其抗番茄斑萎病毒（TSWV）的活性进行了评估。建立了三维定量构效关系（3D-QSAR）分析，根据 CoMFA 和 CoMSIA 模型的分析结果设计并合成了化合物 。生物测定结果表明，化合物 对 TSWV 具有优异的失活活性，EC 值为 144 g/mL，优于宁南霉素（149 g/mL）和先导化合物香豆硫素（525 g/mL）。通过微量热泳动（MST）测试了化合物 与 TSWV CP 的结合能力，结合常数值为 4.4 M，优于宁南霉素（6.2 M）和香豆硫素（59.1 M）。因此，本研究表明，含 4(3)-喹唑啉酮嘧啶环的新型二硫缩醛衍生物可能作为新型抗病毒剂应用。
