Citation: Cheng Hua, Fu Yan, Chang Qing, Zhang Ni, Bu Mengwei, Niu Yan, Wu Qiongyou, Chen Cheng, Verpoort Francis. Synthesis, biochemical evaluation and computational simulations of new cytochrome bc₁ complex inhibitors based on N-(4-aryloxyphenyl) phthalimides[J]. Chinese Chemical Letters, ;2018, 29(12): 1897-1900. doi: 10.1016/j.cclet.2018.10.008 shu

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

Cheng Hua ^a ,
Fu Yan ^a ,
Chang Qing ^a ,
Zhang Ni ^e ,
Bu Mengwei ^a ,
Niu Yan ^c ,
Wu Qiongyou ^c ,
Chen Cheng ^b,*, ,
Verpoort Francis ^b,d,*,

a.
Department of Chemical Engineering and Food Science, Hubei University of Arts and Science, Xiangyang 441053, China
b.
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China
c.
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China
d.
National Research Tomsk Polytechnic University, Tomsk 634050, Russian Federation
e.
Hubei University of Technology Engineering and Technology College, Wuhan 430068, China

chengchen@whut.edu.cn

Francis.Verpoort@ghent.ac.kr

Received Date: 26 August 2018
Revised Date: 30 September 2018
Accepted Date: 9 October 2018
Available Online: 10 December 2018

Figures(4)

The cytochrome bc₁ complex (the bc₁ complex 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 bc₁ complex-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 bc₁ complex). Further studies confirmed that 3e′, a representative compound in this paper, was identified as an inhibitor of the bc₁ complex. Furthermore, computational simulations were also performed to better understand binding of 3e′ to the enzyme complex, which indicated that 3e′ should bind to the Q_o site of the bc₁ complex. Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc₁ complex inhibitors.
- Cytochrome bc₁ complex,
- Inhibitor,
- N-(4-Aryloxyphenyl)phthalimide,
- Synthesis,
- Biochemical evaluation,
- Computational simulation
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Synthesis, biochemical evaluation and computational simulations of new cytochrome bc1 complex inhibitors based on N-(4-aryloxyphenyl) phthalimides

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通讯作者: 陈斌, bchen63@163.com

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