The therapeutic value of thiazole and thiazolidine derivatives in Alzheimer's disease: a systematic literature review

Abstract

Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease and the fifth leading cause of death among the elderly. The development of drugs for AD treatment is based on inhibiting cholinesterase (ChE) activity and inhibiting amyloid-beta peptide and tau protein aggregations. Many in vitro findings have demonstrated that thiazole-and thiazolidine-based compounds have a good inhibitory effect on ChE and other elements involved in the AD pathogenicity cascade.

Experimental approach: In the present review, we collected available documents to verify whether these synthetic compounds can be a step forward in developing new medications for AD. A systematic literature search was performed in major electronic databases in April 2021. Twenty-eight relevant in vitro and in vivo studies were found and used for data extraction.

Findings/results: Findings demonstrated that thiazole-and thiazolidine-based compounds could ameliorate AD's pathologic condition by affecting various targets, including inhibition of ChE activity, amyloid-beta, and tau aggregation in addition to cyclin-dependent kinase 5/p25, beta-secretase-1, cyclooxygenase, and glycogen synthase kinase-3β.

Conclusion and implications: Due to multitarget effects at micromolar concentration, this review demonstrated that these synthetic compounds could be considered promising candidates for developing anti-Alzheimer drugs.

Keywords: Alzheimer's disease; Amyloid beta; Cholinesterase; Glycogen synthase kinase; Thiazole.; Thiazolidine.

Scheme 1.

Enzymes and targets of AD pathogenesis. AD, Alzheimer disease; CDK, cyclin dependent kinase; GSK glycogen synthase kinase; ChE, cholinesterase; BACE, β-site amyloid precursor protein cleaving enzyme; APP, amyloid precursor protein; Aβ, amyloid-beta; TZD, thiazolidines.

Fig. 1.

Selection of articles based on inclusion criteria.