Abstract

Alzheimer’s is a neurodegenerative pathology. The first therapeutic strategy for the treatment of AD was mainly acetylcholinesterase inhibitors (AChEIs) such as Tacrine; a linear tricyclic compound that occupies an important place in the treatment of this disease with its properties pharmacophore. In this regard, the development of tacrine-analogs more efficient and safe with new measures and investigations has drawn immense attention. Various structural modifications of Tacrine have been carried out on different parts. Mainly some modification in the ring structure of tacrine or by connecting the amino group with different hybrids based on natural or synthetic compounds and drugs already in existence. These tacrine congeners have considerable potential for the development of new drugs for the treatment of Alzheimer's disease. Therefore, this review presents an overview of the most important structural modifications in tacrine rings based on the current trends reported in recent decades towards the use of natural products and synthetic analogs as a source of new anti-Alzheimer drugs.

Keywords: Tacrine, tetrahydroacridine, Friedländer reaction, Tacrine homo- and heterodimers, cholinesterase inhibitors, multi-targetdirected ligands (MTDLs), Alzheimer's disease, hepatotoxicity.

Graphical Abstract