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

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 5a exhibited good fungicidal activity against Pseudoperonspera
cubensis in vivo with an inhibition rate of 100% at 100 μg/mL.
A field experiment indicated that the difference of efficacy between 5a (75.9%) and dimethomorph (77.1%) at 37.5 g ai/667 m2 was not significant; and 5a also exhibited good
activity against Botrytis cinerea by triggering accumulation
of PAL and NPR1 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 5a not only showed good fungicidal
activity against P. cubensis but also exhibited plant
innate immunity stimulation activity as a promising fungicide candidate
with both fungicidal activity and systemic acquired resistance.