The Screening And Inhibitory Characterization Of Novel Complex ? Inhibitors And Complex ? Inhibitors

The mitochondrial respiration chain consists of complex I,II,III,IV,the ubiquinone and cyt.c.Complex ? catalyzes the electron via succinic acid to Q.Complex ? catalyzes the electron via QH2 to cyt.c.Complex ?,? are important targets for fungicides discovery.In this master thesis,we studied the complex ?,complex ? and SCR interact with the inhibitors,providing screening platform for discovery of new inhibitors,providing theoretical guidance for the rational design of inhibitors.Therefore we conducted the following work.First,we completed the purification of SCR,and evaluated its properties characterization.Then we studied the screenning and inhibitory characterization of complex ?inhibitors.1.We synthesized 75 pyrazole derivatives.We introduced the structure of coumarin(11 compounds),indole(40 compounds)and benzoxazole(24 compounds).Unfortunately,the 11 compounds containing coumarin structure showed no activity;more exciting is the introduction of the indole structure and benzoxazole structure showed activity;the best active compound is Y14021(IC5O=0.088 ± 0.001 ?M)in indole structures,and the best active compound is Y15312(IC5O=0.038 ± 0.001 ?M)in benzoxazole structures.Their activity are better than the control compound penthiopyrad(IC50=1.321 ± 0.110 ?M)and fluxapyroxad(IC5O=1.124 ± 0.130 ?M).2.We synthesized 44 quinoline derivatives.The best active compound is Y14166(IC50=0.010 ± 0.001 ?M).3.We synthesized 50 thiazole bisamide derivatives.Only four compouns showd activity,the better activity of both compounds were CC207(IC5O=0.321 ± 0.001 ?M)and CC209(IC50=2.757 ± 1.192 ?M),demonstrated the value of further research.4.JFD01971(38%inhibition rate under 100 ?M),AE-848/32004036(46%inhibition rate under 100 ?M)and D436200(IC50=36.216 ± 1.499 ?M)obtained by virtual screening become oue candidate compounds to modify.Last we studied the screenning and inhibitory characterization of complex ?inhibitors.1.We synthesized 14 famoxadone derivatives.The best active compound is Y13364(IC50=0.003 ± 0.001 ?M)in the diphenyl ether structure,the compound's(Y13364)activity is better than the control famoxadone.2.We synthesized 36 Stigmatellin derivatives(three structure types),the best active compound is Y14037(IC50=0.004 ± 0.001?M).3.We synthesized 45 indazole sulfonamide derivatives,in which 21 compounds' activity are better than the control amisulbrom.The best active compound is Y14063(IC50=3.190 ± 0.110 ?M).4.We synthesized 14 benzothiostrobin derivatives.They all showed activity,some are even better than the control Y5247,the best active compound is TWL80(IC50=0.390 ± 0.023 nM).In conclusion,we purified SCR and performed the screenning and inhibitory characterization of novel complex ? inhibitors and complex ?inhibitors,providing comprehensive structure activities relationship for the rational design of potent inhibitors.