A review on tacrine-based scaffolds as multi-target drugs (MTDLs) for Alzheimer's disease

Alzheimer's disease (AD) is a multifactorial neurological disorder among elderly people and combinatorial factors such as genetic, lifestyle, and environmental are involved in onset and disease progression. It has been demonstrated that loss of cholinergic transmission is one of the most significant causes of AD. One strategy currently being investigated for the development of new therapeutics relates to the enhancement of cholinergic system through several ways. At this juncture, anticholinesterase inhibitors have absorbed lots of attention and different marketed drugs such as donepezil, rivastigmine, tacrine, and galantamine have been developed. 9-Amino-1,2,3,4-tetrahydroacridine known as tacrine was introduced in 1945 as an efficient anticholinesterase agent. The mechanism of action of tacrine was proved to inhibit the metabolism of acetylcholine and therefore extending its activity and raising levels in the cerebral cortex. However, extensive use of tacrine was limited since it showed various side effects and toxicity. Thus, lots of efforts were carried out to prepare tacrine analogues to overcome the related adverse effects. This review describes differently synthesized tacrine-based scaffolds as cholinesterase inhibitors to manage Alzheimer's disease (AD).