Synthesis, Anti-Tomato Spotted Wilt Virus Activities, and Interaction Mechanisms of Novel Dithioacetal Derivatives Containing a 4(3H)-Quinazolinone Pyrimidine Ring.

Abstract

A series of unreported novel dithioacetal derivatives containing a 4(3H)-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 D32 was designed and synthesized according to the analysis results of the CoMFA and CoMSIA models. The bioassay results showed that compound D32 exhibited excellent inactivation activity against TSWV, with EC50 values of 144 μg/mL, which was better than those of ningnanmycin (149 μg/mL) and the lead compound xiangcaoliusuobingmi (525 μg/mL). The binding ability of compound D32 to TSWV CP was tested by microscale thermophoresis (MST), and the binding constant value was 4.4 μM, which was better than those of ningnanmycin (6.2 μM) and xiangcaoliusuobingmi (59.1 μM). Therefore, this study indicates that novel dithioacetal derivatives containing a 4(3H)-quinazolinone pyrimidine ring may be applied as new antiviral agents.