Synthesis And Biological Evaluation Of Novel Indole Derivants As Mitochondrial Respiratory Complex Ⅱ Inhibitors

The cytochrome complex II of mitochondrial respiratory chain, called succinate dehydrogenase, is a very important enzyme in the process of mitochondrial respiration. The inhibition of this enzyme can lead to cell energy shortage caused by respiration obstruction, and then to death. During the past 40 years, more attention has been paid to the inhibitors of cytochrome complex II for their unique mechanism. As a result, a series of excellent fungicide with wide antifungal spectrum, high activity and low toxicity have been developed. Nowdays, with the anticipation of obtaining novel and highly effective fungicides, researchers are still focusing on development of inhibitors of cytochrome complex Ⅱ.Inspired by previous reports, this thesis analysed the structure characteristics of cytochrome complex Ⅱ inhibitors. Then, we introduced an indole structure, which has high biological activities as reported, into the inhibitor to obtain a series of novel compound by active structural stitching.This thesis also studied the biological activity of synthesized compounds, and got 10 compounds whose in vitro activity was higher or as good as that of a commercial inhibitor named penthiopyrad and fluxapyroxad. For example, the IC50 of compound Y14021 is 0.09±0.01 μM, and its activity is 10-fold higher than that of penthiopyrad and fluxapyroxad.