Design, Synthesis and Fungicidal Activity of Ester Derivatives of 4-(3,4-Dichloroisothiazole) 7-Hydroxy Coumarin

Abstract

The development of new fungicides is vital for safeguarding crops and ensuring sustainable agriculture. Building on our previous finding that 4-(3,4-dichloroisothiazole)-7-hydroxy coumarins can be used as fungicidal leads, 44 novel coumarin ester derivatives were designed and synthesized to evaluate whether esterification could enhance their fungicidal activity. In vitro fungicidal bioassays indicated that compound 2ai displayed good activity against Alternaria solani, Botrytis cinereal, Cercospora arachidicola, Physalospora piricola and Sclerotinia sclerotiorum, with an EC50 value ranging from 2.90 to 5.56 μg/mL, comparable to the lead compound 1a, with its EC50 value ranging from 1.92 to 9.37 μg/mL. In vivo bioassays demonstrated that compounds 1a, 2ar and 2bg showed comparable, excellent efficacy against Pseudoperonospora cubensis at a dose of 25 µg/mL. Our research shows that the esterification of 4-(3,4-dichloroisothiazole) 7-hydroxycoumarins results in a fungicidal activity equivalent to that of its lead compounds. Furthermore, our density functional theory (DFT) calculations and 3D-QSAR modeling provide a rational explanation of the structure–activity relationship and offer valuable insights to guide further molecular design.

Design and Synthesis of Pyrimidine Amine Containing Isothiazole Coumarins for Fungal Control

“…Any compounds with inhibitions over 70% were chosen for further median effective concentration (EC 50 ) determination according to reported procedures. 27 Molecular Docking. Since the crystal structure of complex I NADH oxidoreductase from fungi has not yet been reported.…”

“…solani, and Sclerotinia sclerotiorum, were sustainably cultured in our laboratory. Any compounds with inhibitions over 70% were chosen for further median effective concentration (EC 50 ) determination according to reported procedures …”

“…Any compounds with inhibitions over 70% were chosen for further median effective concentration (EC 50 ) determination according to reported procedures. 27 …”