Synthesis And Bioactivity Of Mitochondrial Respiratory Complex Ⅱ Inhibitors

Succinate dehydrogenase, also known as mitochondrial respiratory chain complex Ⅱ,is a very important enzyme in mitochondrial respiration that catalyzes the oxidation of succinate to fumarate. The oxidation is coupled to reduction of ubiquinone to ubiquinol at the same time. This kind of inhibitors act on fungal mitochondrial respiratory chain complex Ⅱ, preventing the electron transport, affecting the energy metabolism,eventually leading to the death of fungi.Though literature research, this thesis briefly described the structure of the mitochondrial respiratory chain, and introduced the mode of action and research progress of complex Ⅱ. Based on the pharmacophore-linked fragment virtual screening (PFVS)and the principle of combination of active groups, we designed and synthesized three series of 50 compounds. All target compounds were characterized by 1H NMR, GC-MS,and elemental analysis. The structures of these compounds are summarized as follows:The biological activity of these compounds was also studied, and we got a series of compounds having good enzyme activity. For example, the IC50 of compound Y14166 is 0.010 ±0.001μM, which raises more than 130 times than the commercial fungicide penthiopyrad whose IC50 is 1.321±0.11 μM.