Synthesis, Biological Evaluation and Molecular Docking Studies of Piperidinylpiperidines and Spirochromanones Possessing Quinoline Moieties as Acetyl-CoA Carboxylase Inhibitors

Molecules

Tonghui Huang¹  Jie Sun¹  Qianqian Wang²  Jian Gao²  Yi Liu² 

[1] Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China;

关键词: acetyl-CoA carboxylase;    inhibitors;    piperidinylpiperidines;    spirochromanones;    synthesis;    molecular docking;   

DOI  :  10.3390/molecules200916221

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.