Design, Synthesis, and Anti-ToCV Activity of Novel Pyrimidine Derivatives Bearing a Dithioacetal Moiety that Targets ToCV Coat Protein

Abstract

Novel pyrimidine sulfide derivatives containing a dithioacetal and strobilurin moiety were designed and synthesized. Their antiviral activities against tomato chlorosis virus (ToCV) were investigated through the tomato chlorosis virus coat protein (ToCVCP)-oriented screening method. Microscale thermophoresis was used to study the interaction between the compound and the ToCVCP. Compounds <b>B13</b> and <b>B23</b> interacted better with ToCVCP than the other compounds and had dissociation constant (<i>K</i>_d) values of 0.09 and 0.06 μM, respectively. These values were lower than those of the control agents, <b>ningnanmycin</b> (0.19 μM) and <b>ribavirin</b> (6.54 μM), which indicated that the compounds had a strong binding effect with ToCVCP. Quantitative real-time polymerase chain reaction was used to evaluate the role of compounds <b>B13</b> and <b>B23</b> in the gene regulation of ToCVCP. Both compounds significantly reduced the expression level of the ToCVCP gene in <i>Nicotiana benthamiana</i> with reduction values of 88 and 83%, which were better than those of <b>ningnanmycin</b> (65%) and lead compound <b>C14</b> (73%). Pyrimidine sulfide containing a dithioacetal and strobilurin moiety is significant in the research and development of novel anti-ToCV agents.