Inhibition Kinetics Studies Of Mitochondrial Complex â…¡ And Complex â…¢ Inhibitors

Mitochondria is the important place for cellular respiration of eukaryotic cells. The mitochondrial respiration chain is located on the inner membrane and comprising of four large trans-membrane protein complexes (Complex Ⅰ, Ⅱ, Ⅲ and Ⅳ) as well as ubiquinone between Complex Ⅰ/Ⅱ and Ⅲ and cytochrome c between Complex Ⅲ and Ⅳ. The function of mitochondrial respiration chain is biological oxidation which is coupled with phosphorylation by Complex V and complete producing energy ATP.SCR composed by complex Ⅱ and Ⅲ. Complex Ⅱ catalyzes electron transfer from succinate to Q, and complex III catalyzes electron transfer from QH2to cyt c while translocating protons across the inner mitochondrial membrane. Both complex Ⅱ and Ⅲ can used to target for fungicides.We established the extraction and purification of succinate-ubiquinone reductase, and evaluated its purity and activity. We researched the structural biology of SCR.We studied the inhibitors to target to complex Ⅱ and the inhibitor kinetics. We determined the activity and mode of action for ten commercial inhibitors of complex Ⅱ. We synthesized23new compounds, but those compounds cannot inhibit the activity of complex Ⅱ nearly with commercial inhibitors.We studied the inhibitors to target to complex Ⅲ and the inhibitor kinetics. One、To the parent design Famoxadone synthesized28new oxazolidinedione derivatives activity test,which compounds Y12313(12.27nM)和Y12043(6.71nM) activity was slightly worse than Famoxadone. Two、Indazole sulfonamide mother designed and synthesized18new compounds active test and found that the inhibitory activity of these compounds100μM are very low, even the commercialization of the indazole sulfonamide100μM at only45%. Three、With oct-1-y1MEPANIPYRIM29new synthetic compound precursor design (four structural type) activity test, the former three types of active compound, but the activity was much greater than oct-oxazole MEPANIPYRIM structure IVthe compounds active Sim azole mEPANIPYRIM equal to or even slightly better than, the value of further。To sum up, we purified succinate-ubiquinone reductase. Furthermore, we studied the inhibitor kinetics of the complex Ⅱ and complex Ⅲ inhibitors. The results would shed light on the research of inhibitor with high activity and new structure.