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线粒体呼吸链复合体II(EC 1.3.5.1)又称为线粒体琥珀酸脱氢酶(succinate dehydrogenase,SDH)和琥珀酸-泛醌氧化还原酶(succinate:ubiquinone oxidoreductase,SQR),它是一种重要的杀菌剂靶标,作用于该靶标的商业化品种已有19个.本文以本课题组前期通过虚拟筛选得到的先导化合物为起点,设计并合成了一系列新型的N-(1-苯胺基-2,2,2-三氯乙基)-1H-吡唑酰胺类化合物4a~4z和5,其中化合物4r和5对猪心来源SQR的半抑制浓度(IC_(50)值)分别达到了0.106μM和15.01nM.采用分子模拟技术研究了它们的构效关系,结合自由能的理论计算值(△G_(cal))与实验测定值(△G_(exp))之间的相关性(R~2)为0.95,表明基于分子对接得到的结合模式是可信的,化合物活性的提高在很大程度依赖于侧链部分与受体的相互作用能的提高.
Mitochondrial respiratory chain complex II (EC 1.3.5.1), also known as mitochondrial succinate dehydrogenase (SDH) and succinate (ubiquinone oxidoreductase, SQR), is an important Of the fungicide target, the commercialization of the target species has 19. In this paper, the pilot group by the virtual screening of lead compounds as a starting point to design and synthesis of a series of new N- (1 - anilino - Trichloroethyl) -1H-pyrazole amide compounds 4a-4z and 5, in which the half-inhibitory concentrations (IC 50) of compounds 4r and 5 on porcine heart SQR reached 0.106 μM and 15.01nM, respectively. Their structure-activity relationship was studied by molecular simulation. The correlation between the calculated value of free energy (ΔG_ (cal)) and the experimental value (ΔG_ (exp) 2) was 0.95, indicating that the binding mode obtained on the basis of the molecular docking is credible, and the improvement of the activity of the compound largely depends on the increase of the interaction energy between the side chain moiety and the acceptor.