Tacrine-Based Hybrids: Past, Present, and Future

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jan 21

PMID 36675233

Authors

Anna Bubley

Alexaner Erofeev

Peter Gorelkin

Elena Beloglazkina

Alexander Majouga

Olga Krasnovskaya

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by β-amyloid (Aβ) aggregation, τ-hyperphosphorylation, and loss of cholinergic neurons. The other important hallmarks of AD are oxidative stress, metal dyshomeostasis, inflammation, and cell cycle dysregulation. Multiple therapeutic targets may be proposed for the development of anti-AD drugs, and the "one drug-multiple targets" strategy is of current interest. Tacrine (THA) was the first clinically approved cholinesterase (ChE) inhibitor, which was withdrawn due to high hepatotoxicity. However, its high potency in ChE inhibition, low molecular weight, and simple structure make THA a promising scaffold for developing multi-target agents. In this review, we summarized THA-based hybrids published from 2006 to 2022, thus providing an overview of strategies that have been used in drug design and approaches that have resulted in significant cognitive improvements and reduced hepatotoxicity.

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