N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide: A new dual-target inhibitor of mitochondrial complex II and complex III via structural simplification |
| |
| Institution: | 1. Department of Chemical Engineering and Food Science, Hubei University of Arts and Science, Xiangyang 441053, PR China;2. State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, PR China;3. Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China;1. School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152 – 160 Pearse Street Trinity College Dublin, Dublin 2, Ireland;2. School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, 152 – 160 Pearse Street Trinity College Dublin, Dublin 2, Ireland;3. School of Biological and Health Sciences, Technology University Dublin, Dublin City Campus, Kevin St., Dublin 8 D08 NF82, Ireland;4. School of Chemistry, Trinity College Dublin, Dublin 2, Ireland;1. Sequoia Sciences, Inc., 1912 Innerbelt Business Center Drive, St. Louis, MO 63114, United States;2. Albany Molecular Research Inc., 1001 Main Street, Buffalo, NY 14203, United States;1. Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China;2. Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China;3. State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China;1. Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Chemical Biology Center, Central China Normal University, Wuhan 430079, PR China;2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300071, PR China;1. Key Laboratory of Theoretical Organic Chemistry and Functional Molecular, Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, People’s Republic of China;2. Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, People’s Republic of China;1. College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China;2. Zhejiang Base of National Southern Pesticide Research Centre, Zhejiang Research Institute of Chemical Industry, Hangzhou 310023, China |
| |
| Abstract: | Mitochondrial complex II and complex III are two promising targets for the development of numerous pharmaceuticals and pesticides. Although tremendous inhibitors of either complex II or complex III were identified, compounds which are capable of prohibiting the activities of both complexes have been rarely reported. Since multi-target drugs can interact with several drug targets simultaneously, we were keen on discovering new and potent dual-target inhibitors of both complex II and complex III. Therefore, a new series of structurally simplified sulfonamides bearing a diaryl ether scaffold were designed and synthesized in this paper. Afterwards, the biological activities of the newly synthesized compounds were evaluated. The results implied that several compounds demonstrated outstanding potency against succinate-cytochrome c reductase (SCR, a mixture of complex II and complex III). Further studies confirmed that N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide (3f), a representative compound herein, was identified as a dual-target inhibitor of both complexes. Furthermore, computational simulations were also performed to have a better understanding about binding of 3f to the enzyme complexes, which concluded that 3f should bind to complex II and the Qo site of complex III. Consequently, we harbor the idea that this work can be beneficial for the synthesis and discovery of more dual- or multi-target inhibitors. |
| |
| Keywords: | Dual-target inhibitor Diaryl ether Sulfonamide Mitochondrial complex II and complex III Structural simplification |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
