Discovery of Novel 3,4-Dichloroisothiazole-Containing Coumarins as Fungicidal Leads.

Natural products are one of the resources for discovering novel fungicidal leads. As a natural fungicide, osthole was used as a coumarin-based lead compound for the development of novel fungicides. Here, a series of 3,4-dichloroisothiazole-containing 7-hydroxycoumarins were rationally designed, synthesized, and characterized by introducing a bioactive substructure, 3,4-dichloroisothiazole, into the coumarin skeleton. bioassay indicated that compound displayed good activity against , , , and . Its median effective concentration (EC) value against each of these fungi fell between 0.88 and 2.50 μg/mL, which was much lower than that of osthole against the corresponding pathogen (between 7.38 and 74.59 μg/mL). screening validated that exhibited 100%, 60%, and 20% efficacy against Kühn at 200, 100, and 50 μg/mL, respectively. RNA sequence analysis implied that growth inhibition of by might result from potential disruptions of fungal membrane formation and intracellular metabolism. Furthermore, a field experiment with cucumber plants indicated that showed 62.73% and 74.03% efficacy against (Berk. & Curt.) Rostov. at rates of 12.5 g a.i./ha and 25 g a.i./ha, respectively, which showed no significant difference between and osthole at 30 g a.i./ha. Our studies suggested that , , and might be used as fungicidal leads for further optimization.