Coumarin Derivatives Containing Sulfonamide and Dithioacetal Moieties: Design, Synthesis, Antiviral Activity, and Mechanism

Cucumber mosaic virus (CMV) is currently
a known plant virus with
the most hosts, broadest distribution, and economic hazard. To develop
new antiviral drugs against this serious virus, a new range of coumarin
derivatives containing sulfonamide and dithioacetal structures were
designed and synthesized, and their anti-CMV activities were detected
by the half-leaf dead spot method. The results of the biological activity
assay showed that most of the compounds exhibited outstanding anti-CMV
activity. Especially, compound C23 displayed the optimal
in vivo anti-CMV activity, with an EC50 value of 128 μg/mL,
which was remarkably better than that of COS (781 μg/mL) and
ningnanmycin (436 μg/mL). Excitingly, we found that compound C23 could be a promising plant activator that significantly
increased defense-related enzyme activities and the tobacco chlorophyll
content. Furthermore, compound C23 enhanced defense responses
against viral infection by inducing the abscisic acid (ABA) pathway
in tobacco. This work established a basis for multifunction pesticide
discovery involving mechanism of action study and structure optimization.