Discovery of Novel Thiazole Carboxamides as Antifungal Succinate Dehydrogenase Inhibitors

To contribute molecular diversity
for novel fungicide development,
a series of novel thiazole carboxamides were rationally designed,
synthesized, and characterized with the succinate dehydrogenase (SDH)
as target. Bioassay indicated that compound 6g showed
the similar excellent SDH inhibition as that of Thifluzamide with
IC50 of 0.56 mg/L and 0.55 mg/L, respectively. Some derivatives
displayed improved in vitro fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum with EC50 of 1.2–16.4 mg/L and 0.5–1.9
mg/L. Surprisingly, 6g showed promising in vitro fungicidal activities against R. cerealis and S. sclerotiorum with EC50 of 6.2 and 0.6 mg/L, respectively, which was superior to
Thifluzamide with the EC50 of 22.1 and 4.4 mg/L, respectively.
Additionally, compounds 6c and 6g displayed
excellent in vivo fungicidal activities against S. sclerotiorum on Brassica napus L. leaves with protective activity
of 75.4% and 67.3% at 2.0 mg/L, respectively, while Thifluzamide without
activity at 5.0 mg/L. Transcriptomic analysis of S. sclerotiorum treated with 6g by RNA sequencing indicated the down-regulation
of succinate dehydrogenase gene SDHA and SDHB, and the inhibition
of the TCA-cycle.