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 B13 and B23 interacted better with ToCVCP than the other compounds and had dissociation constant (K d) values of 0.09 and 0.06 μM, respectively. These values were lower than those of the control agents, ningnanmycin (0.19 μM) and ribavirin (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 B13 and B23 in the gene regulation of ToCVCP. Both compounds significantly reduced the expression level of the ToCVCP gene in Nicotiana benthamiana with reduction values of 88 and 83%, which were better than those of ningnanmycin (65%) and lead compound C14 (73%). Pyrimidine sulfide containing a dithioacetal and strobilurin moiety is significant in the research and development of novel anti-ToCV agents.

Review on Structures of Pesticide Targets

“…For example, harpin binding protein-1 is a potential target activated antiviral response in tobacco by antiviral agent dufulin [ 81 ], and tomato chlorosis virus (ToCV), CP play significant roles in sustaining the methyl cycle and S-adenosylmethionine-dependent methyltransferase activity and its minor CP play important roles in silencing suppression activity to counteract the RNA silencing-mediated defense response of the host [ 82 , 83 ]. Glucopyranoside derivatives, pyrimidine derivatives, 4(3H)-quinazolinone derivatives, and novel quinazolinone sulfide inhibitors targets ToCV coat protein with high anti-ToCV activity [ 84 , 85 , 86 , 87 ], and its minor coat protein is regarded as a novel target for the new green anti-ToCV inhibitors [ 88 ].…”

Recent achievements on the agricultural applications of thioether derivatives: A 2010–2020 decade in review

“…Furthermore, TEM results showed compound 121 can destroy the integrity of TMV-CP, combine with TMV-CP, and hydrolyze TMV-CP to impact the process of self-assembling of TMV with the K d value of 4.5 mg/L. The same year, Zan and coworkers [123] designed and synthesized a series of pyrimidine sulfide derivatives containing dithioacetal and strobilurin moieties. MST results showed that compounds 122 and 123 (Figure 36) interacted better with ToCV-CP than the other compounds and had K d values of 0.09 and 0.06 μM, respectively, which were even better than those of Ningnanmycin and Ribavirin.…”

Synthesis and Antifungal Activity of Pyrimidine Derivatives Containing an Amide Moiety

“…Pyrimidines are important substances in the synthesis of various active molecules that are extensively used in the intermediate skeleton of agrochemicals ( Chen et al, 2015 ; Wu et al, 2015 ) and have attracted more and more attention due to their extensive biological activities ( Sun et al, 2006 ), including antiviral ( Wu et al, 2016a ), antibacterial ( Wu et al, 2016b ), antifungal ( Wu et al, 2019 , 2020 ), and insecticidal ( Liu et al, 2017 ; Wu et al, 2020 ) activities. For example, Zan et al reported pyrimidine derivatives bearing a dithioacetal moiety as effective antiviral agents for controlling the tomato chlorosis virus (ToCV) ( Zan et al, 2021 ). Zhang et al found a series of arylpyrazole pyrimidine ether derivatives with promising bioactivity for combating cucumber downy mildew ( Zhang et al, 2019 ).…”