Discovery of Novel Isothiazole, 1,2,3-Thiadiazole, and Thiazole-Based Cinnamamides as Fungicidal Candidates

Abstract

A series of isothiazole, 1,2,3-thiadiazole, and thiazole-based cinnamamide morpholine derivatives were rationally designed, synthesized, characterized, and evaluated for their fungicidal activities. Bioassay indicated that a combination of 3,4-dichloroisothiazole active substructures with cinnamamide morpholine lead to significant improvement of in vivo antifungal activities of the target compounds; among them, compound <b>5a</b> exhibited good fungicidal activity against <i>Pseudoperonspera cubensis</i> in vivo with an inhibition rate of 100% at 100 μg/mL. A field experiment indicated that the difference of efficacy between <b>5a</b> (75.9%) and dimethomorph (77.1%) at 37.5 g ai/667 m² was not significant; and <b>5a</b> also exhibited good activity against <i>Botrytis cinerea</i> by triggering accumulation of <i>PAL</i> and <i>NPR1</i> defense-related gene expression and the defense associated enzyme phenylalanine ammonia-lyase (PAL) expression on cucumber, rather than direct inhibition. These findings strongly supported that 3,4-dichloroisothiazole containing cinnamamide morpholine <b>5a</b> not only showed good fungicidal activity against <i>P. cubensis</i> but also exhibited plant innate immunity stimulation activity as a promising fungicide candidate with both fungicidal activity and systemic acquired resistance.