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

Yao Chen; Yaoyao Bian; Yuan Sun; Chen Kang; Sheng Yu; Tingming Fu; Wei Li; Yuqiong Pei; Haopeng Sun

doi:10.7717/peerj.2140

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

PeerJ. 2016 Jul 7:4:e2140. doi: 10.7717/peerj.2140. eCollection 2016.

Authors

Yao Chen¹, Yaoyao Bian², Yuan Sun³, Chen Kang⁴, Sheng Yu⁵, Tingming Fu¹, Wei Li⁵, Yuqiong Pei⁵, Haopeng Sun⁶

Affiliations

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.
² School of Nursing, Nanjing University of Chinese Medicine , Nanjing , China.
³ Department of Chemistry and Biochemistry, Ohio State University , Columbus , OH , United States.
⁴ Division of Pharmacology, College of Pharmacy, Ohio State University , Columbus , OH , United States.
⁵ School of Pharmacy, Nanjing University of Chinese Medicine , Nanjing , China.
⁶ Department of Medicinal Chemistry, China Pharmaceutical University , Nanjing , China.

Abstract

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.

Keywords: 4-aminoquinoline core; AChEIs; Inhibitor design.

Grants and funding

The study was supported from grants 81402851 and 81573281 of the National Natural Science Foundation of China and BK20140957 of Natural Science Foundation of Jiangsu Province. We also received support from the Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP-PPZY2015A070) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.