Identification of 4-aminoquinoline core for the design of new cholinesterase inhibitors

• Main Authors: Yao Chen, Yaoyao Bian, Yuan Sun, Chen Kang, Sheng Yu, Tingming Fu, Wei Li, Yuqiong Pei, Haopeng Sun
• Format: Article
• Language: English
• Published: PeerJ Inc. 2016-07-01
• Series: PeerJ
• Subjects: AChEIs; Inhibitor design; 4-aminoquinoline core
• Online Access: https://peerj.com/articles/2140.pdf

Inhibition of acetylcholinesterase (AChE) using small molecules is still one of the most successful therapeutic strategies in the treatment of Alzheimer’s disease (AD). Previously we reported compound T5369186 with a core of quinolone as a new cholinesterase inhibitor. In the present study, in order to identify new cores for the designing of AChE inhibitors, we screened different derivatives of this core with the aim to identify the best core as the starting point for further optimization. Based on the results, we confirmed that only 4-aminoquinoline (compound 04 and 07) had cholinesterase inhibitory effects. Considering the simple structure and high inhibitory potency against AChE, 4-aminoquinoline provides a good starting core for further designing novel multifunctional AChEIs.