Discovery of novel chromone derivatives containing a sulfonamide moiety as potential anti-TSWV agents

Bioorg Med Chem Lett. 2021 Dec 1:53:128431. doi: 10.1016/j.bmcl.2021.128431. Epub 2021 Oct 28.

Abstract

A number of chromone derivatives containing sulfonamide structure were designed and synthesized. Firstly, the target compounds were evaluated for anti-TSWV activities in vivo by the half-leaf method. We found that most of the compounds had good anti-TSWV activities. Among them, compound 12B had excellent anti-TSWV inactivating activity with an EC50 of 80.5 μg/mL, which was significantly better than xiangcaoliusuobingmi (765.7 μg/mL). Secondly, TSWV nucleocapsid protein (N) was expressed and purified, and the affinity between the compounds and TSWV N was tested by microscale thermophoresis (MST). Compound 12B had a good affinity for TSWV N with a Kd value of 5.02 μM, which was superior to xiangcaoliusuobingmi (29.83 μM). Finally, in order to study the mode of interaction between the compound 12B and TSWV N, we carried out molecular docking. The results indicated that compound 12B might inactivate the virus by destroying the TSWV N oligomer structure. These results lay a solid foundation for the further discovery of chromone derivatives containing sulfonamide structure with high anti-TSWV activities.

Keywords: Anti-TSWV activity; Chromone derivatives; Microscale thermophoresis; Molecular docking; Sulfonamide structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Chromones / chemical synthesis
  • Chromones / chemistry
  • Chromones / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Tospovirus / drug effects*

Substances

  • Antiviral Agents
  • Chromones
  • Sulfonamides