Discovery of Potent and Novel Quinazolinone Sulfide Inhibitors with Anti-ToCV Activity

A series of novel quinazolinone sulfide derivatives containing a dithioacetal moiety were designed and synthesized using Tomato chlorosis virus coat protein (ToCVCP) as a potential drug target, and the inhibitory effect of ToCV was systematically evaluated in vitro and in vivo. The experimental results showed that most of the compounds presented a strong affinity. Notably, the binding abilities of compounds D8 and D16 to ToCVCP both reached a micromolar level, which were 0.19 and 0.83 μM, respectively. The relative expression level of ToCVCP gene was detected using real-time quantitative polymerase chain reaction in Nicotiana benthamiana. Compounds D8 and D16 significantly reduced the relative expression level of ToCVCP gene by 93.34 and 83.47%, respectively, which were better than those of conventional antiviral agents. This study lays a good foundation for the structural design and modification of quinazolinone sulfide derivatives as anti-ToCV drugs.