Discovery of Novel Chromone Derivatives Containing a Sulfonamide Moiety as Anti-ToCV Agents through the Tomato Chlorosis Virus Coat Protein-Oriented Screening Method

Abstract

A number of novel chromone derivatives containing sulfonamide moieties were designed and synthesized, and the activity of compounds against tomato chlorosis virus (ToCV) was assessed using the ToCVCP-oriented screening method. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were established based on the dissociation constant (<i>K</i>_d) values of the target compounds, and compound <b>35</b> was designed and synthesized with the aid of CoMFA and CoMSIA models. The study of affinity interaction indicated that compound <b>35</b> exhibited excellent affinity with ToCVCP with a <i>K</i>_d value of 0.11 μM, which was better than that of the positive control agents xiangcaoliusuobingmi (0.44 μM) and ningnanmycin (0.79 μM). In addition, the <i>in vivo</i> inhibitory effect of compound <b>35</b> on the ToCVCP gene was evaluated by the quantitative real-time polymerase chain reaction. ToCVCP gene expression levels of the compound <b>35</b> treatment group were reduced by 67.2%, which was better than that of the positive control agent ningnanmycin (59.5%). Therefore, compound <b>35</b> can be used as a potential anti-ToCV drug in the future.