Synthesis,biochemical evaluation and computational simulations of new cytochrome bc1 complex inhibitors based on N-(4-aryloxyphenyl)phthalimides

作     者：Hua Cheng Yan Fu Qing Chang Ni Zhang Mengwei Bu Yan Niu Qiongyou Wu Cheng Chen Francis Verpoort 

作者机构：Department of Chemical Engineering and Food ScienceHubei University of Arts and ScienceXiangyang 441053China State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of TechnologyWuhan 430070China Key Laboratory of Pesticide&Chemical BiologyMinistry of EducationCollege of ChemistryCentral China Normal UniversityWuhan 430079China National Research Tomsk Polytechnic UniversityTomsk 634050Russian Federation Hubei University of Technology Engineering and Technology CollegeWuhan 430068China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2018年第29卷第12期

页      面：1897-1900页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.21502062,21272091 and 21472063) Hubei Provincial Department of Education(No.Q20102606) Xiangyang Science and Technology Bureau(No.2010GG1B33) Structural Biomedicine and Pharmacochemistry of Hubei University of Arts and Science the support from the Russian Foundation for Basic Research(No.18-29-04047) the Tomsk Polytechnic University Competitiveness Enhancement Program grant(No.VIU-195/2018) 

主　　题：Cytochrome bc_1 complex Inhibitor N-(4-Aryloxyphenyl)phthalimide Synthesis Biochemical evaluation Computational simulation 

摘      要：The cytochrome bc1complex(the bc1complex or complex Ⅲ) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out,and the results implied that several compounds demonstrated good activities against succinatecytochrome reductase(SCR, a mixture of mitochondrial complex Ⅱ and the bc1complex). Further studies confirmed that 3e’, a representative compound in this paper, was identified as an inhibitor of the bc1complex. Furthermore, computational simulations were also performed to better understand binding of 3e’ to the enzyme complex, which indicated that 3e’ should bind to the Qosite of the ***, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1complex inhibitors.