Design, Synthesis, and Anti-ToCV Activity of Novel 4(3 H)-Quinazolinone Derivatives Bearing Dithioacetal Moiety

J Agric Food Chem. 2020 May 20;68(20):5539-5544. doi: 10.1021/acs.jafc.0c00086. Epub 2020 May 8.

Abstract

Tomato chlorosis virus (ToCV) has caused great harm to the production of tomato worldwide. To develop efficient anti-ToCV agents, some novel 4(3H)-quinazolinone derivatives containing dithioacetal were designed and synthesized, and their anti-ToCV activities were evaluated by microscale thermophoresis (MST) using ToCV coat protein (ToCV-CP) as a new target. The results showed that some compounds had a strong binding capacity to ToCV-CP. In particular, compounds C5 and C22 have an excellent binding capacity to ToCV-CP, with binding constant values of 0.24 and 0.25 μM, respectively. Additionally, reduced ToCV-CP gene expression levels of 81.05 and 87.59% could be achieved when tomato was treated with compounds C5 and C22, respectively, which were obviously higher than the levels after ningnanmycin (NNM) treatment (43.88%) and lead compound Xiangcaoliusuobingmi (XCLSBM) treatment (63.56%). Therefore, this work indicates that 4(3H)-quinazolinone derivatives containing dithioacetal moiety can be used as novel anti-ToCV agents.

Keywords: 4(3H)-quinazolinone; MST; anti-ToCV activity; coat protein; dithioacetal; tomato chlorosis virus.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Crinivirus / drug effects*
  • Crinivirus / genetics
  • Crinivirus / physiology
  • Drug Design
  • Molecular Structure
  • Plant Diseases / virology
  • Quinazolinones / chemistry*
  • Quinazolinones / pharmacology*
  • Solanum lycopersicum / virology
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Quinazolinones

Supplementary concepts

  • Tomato chlorosis virus