Pharmacological Exploration of Triazole-based Therapeutics for Alzheimer's Disease: An Overview

Abstract

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder that may account for approximately 60-70% of cases of dementia worldwide. AD is characterized by impaired behavioural and cognitive functions, including memory, language, conception, attentiveness, judgment, and reasoning problems. The two important hallmarks of AD are the appearance of plaques and tangles of amyloid-beta (Aβ) and tau proteins, respectively, in the brain based on the etiology of the disease, including cholinergic impairment, metal dyshomeostasis, oxidative stress, and degradation of neurotransmitters. Currently, the used medication only provides alleviation of symptoms but is not effective in curing the disease, which creates the need to develop new molecules to treat AD. Heterocyclic compounds have proven their ability to be developed as drugs for the treatment of various diseases. The five-membered heterocyclic compound triazole has received foremost fascination for the discovery of new drugs due to the possibility of structural variation. Moreover, it has proved its significance in various drug categories. This review mainly summarizes the recent advancements in the development of novel 1,2,3-triazole and 1,2,4-triazole-based molecules in the drug discovery process for targeting various AD targets such as phosphodiesterase 1 (PDE1) inhibitors, apoptosis signal-regulating kinase 1 (ASK1) inhibitors, somatostatin receptor subtype-4 (SSTR4) agonist, several other druggable targets, molecular modelling studies, as well as various methodologies for the synthesis of triazoles containing molecules such as click reaction, Pellizzari reaction, and Einhorn- Brunner reaction.

Keywords: 1; 2; 3-triazole; 4-triazole; Alzheimer’s disease; Aβ-amyloid; Pellizzari reaction; molecular docking; phosphodiesterase 1 inhibitors; tau proteins.