Design, Synthesis, and Biological Activity of Silicon-Containing Carboxamide Fungicides.

Bioisosteric silicon replacement has proven to be a valuable strategy in the design of bioactive molecules for crop protection and drug development. Twenty-one novel carboxamides possessing a silicon-containing biphenyl moiety were synthesized and tested for their antifungal activity and succinate dehydrogenase (SDH) enzymatic inhibitory activity. Among these novel succinate dehydrogenase inhibitors (SDHIs), compounds , , and possessing appropriate log and topological polar surface area values showed excellent inhibitory effects against , , , and at 10 mg/L in vitro, and the EC values of and were 0.52 and 0.16 mg/L against and 0.066 and 0.054 mg/L against , respectively, which were superior to those of Boscalid. Moreover, compound demonstrated superior SDH enzymatic inhibitory activity (IC = 8.70 mg/L), exhibiting 2.54-fold the potency of Boscalid (IC = 22.09 mg/L). Docking results and scanning electron microscope experiments revealed similar mode of action between compound and Boscalid. The new silicon-containing carboxamide is a promising SDHI candidate that deserves further investigation.