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

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.