title: Synthesis, Biological Evaluation and Molecular Docking Studies of Piperidinylpiperidines and Spirochromanones Possessing Quinoline Moieties as Acetyl-CoA Carboxylase Inhibitors.
abstract: Acetyl-coenzyme A carboxylases (ACCs) play critical roles in the regulation of fatty acid metabolism and have been targeted for the development of drugs against obesity, diabetes and other metabolic diseases. Two series of compounds possessing quinoline moieties were designed, synthesized and evaluated for their potential to inhibit acetyl-CoA carboxylases. Most compounds showed moderate to good ACC inhibitory activities and compound 7a possessed the most potent biological activities against ACC1 and ACC2, with IC50 values of 189 nM and 172 nM, respectively, comparable to the positive control. Docking simulation was performed to position compound 7a into the active site of ACC to determine a probable binding model.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. hancp@iccas.ac.cn.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. xincheng127@sina.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. ruofei16888@163.com.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. gaojian.gucas@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. cbpeliuyinew@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D010880:Piperidines; D000103:Acetyl-CoA Carboxylase
keywords: acetyl-CoA carboxylase; inhibitors; molecular docking; piperidinylpiperidines; spirochromanones; synthesis