Effects of Linkers and Substitutions on Multitarget Directed Ligands for Alzheimer’s Diseases: Emerging Paradigms and Strategies

Alzheimer’s disease (AD) is multifactorial, progressive and the most predominant cause of cognitive impairment and dementia worldwide. The current “one-drug, one-target” approach provides only symptomatic relief to the condition but is unable to cure the disease completely. The conventional single-target therapeutic approach might not always induce the desired effect due to the multifactorial nature of AD. Hence, multitarget strategies have been proposed to simultaneously knock out multiple targets involved in the development of AD. Herein, we provide an overview of the various strategies, followed by the multitarget-directed ligand (MTDL) development, rationale designs and efficient examples. Furthermore, the effects of the linkers and substitutional functional groups on MTDLs against various targets of AD and their modes of action are also discussed.