Novel multitarget-directed tacrine derivatives as potential candidates for the treatment of Alzheimer's disease

J Enzyme Inhib Med Chem. 2017 Dec;32(1):572-587. doi: 10.1080/14756366.2016.1210139.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder, which is complex and progressive; it has not only threatened the health of elderly people, but also burdened the whole social medical and health system. The available therapy for AD is limited and the efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the design and development of efficacious and safe anti-AD agents has become a hotspot in the field of pharmaceutical research. Due to the multifactorial etiology of AD, the multitarget-directed ligands (MTDLs) approach is promising in search for new drugs for AD. Tacrine, which is the first acetylcholinesterase (AChE) inhibitor, has been selected as the ideal active fragment because of its simple structure, clear activity, and its superiority in the structural modification, thus it could be introduced into the overall molecular skeletons of the multi-target-directed anti-AD agents. In this review, we have summarized the recent advances (2012 to the present) in the chemical modification of tacrine, which could provide the reference for the further study of novel multi-target-directed tacrine derivatives to treat AD.

Keywords: AChE inhibitors; Alzheimer’s disease; multitarget-directed; tacrine.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Cholinesterase Inhibitors / therapeutic use
  • Humans
  • Tacrine / analogs & derivatives
  • Tacrine / therapeutic use*
  • tau Proteins / antagonists & inhibitors

Substances

  • Cholinesterase Inhibitors
  • tau Proteins
  • Tacrine

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81274058, 21302225), Natural Science Foundation of Jiangsu Province (BK20151563), the Program for New Century Excellent Talents by the Ministry of Education (NCET-12?0741), 333 High-level Talents Training Project Funded by Jiangsu Province, Six Talents Project Funded by Jiangsu Province (2013-YY-010), Technology Innovation Venture Fund by Nanjing University of Chinese Medicine (CX201301), Program for Excellent Talents in School of Pharmacy of Nanjing University of Chinese Medicine (15ZYXET-1), Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXMHT-1?13), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions and Project Funded by the Flagship Major Development of Jiangsu Higher Education Institutions (PPZY2015A070), and Key Laboratory of Therapeutic Material of Chinese Medicine, Jiangsu Province.