title: Novel multitarget-directed tacrine derivatives as potential candidates for the treatment of Alzheimer's disease.
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.
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Wu
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Dai
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Nian-Guang
authors.initials: NG
authors.lastname: Li
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Ze-Xi
authors.initials: ZX
authors.lastname: Dong
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Ting
authors.initials: T
authors.lastname: Gu
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|c Department of Organic Chemistry , China Pharmaceutical University , Nanjing , Jiangsu , China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Shi
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xue
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.affiliation: a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.|b Department of Medicinal Chemistry , Nanjing University of Chinese Medicine , Nanjing , Jiangsu , China.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D006801:Humans; D013619:Tacrine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D016875:tau Proteins / Q000037:antagonists & inhibitors
chemical_list: D002800:Cholinesterase Inhibitors; D016875:tau Proteins; D013619:Tacrine
keywords: AChE inhibitors; Alzheimer’s disease; multitarget-directed; tacrine