Acetylcholinesterase Inhibitors from Carbamate and Benzo-fused Heterocyclic Scaffolds: Promising Therapeutics for Alzheimer’s Disease

Abstract

Alzheimer’s disease is the most prevalent type of dementia, characterized by a progressive loss of memory and neurodegeneration that hinders a patient’s ability to perform daily tasks. This paper explores the potential of acetylcholinesterase inhibitors derived from carbamate and benzo-fused heterocyclic scaffolds as potential therapeutics for Alzheimer’s disease. Inhibiting acetylcholinesterase is crucial for enhancing cognitive function in Alzheimer’s patients. The findings indicate that novel compounds featuring the mentioned scaffolds exhibit promising acetylcholinesterase inhibitory efficacy. Several of these compounds display superior half-maximal inhibitory concentration values against acetylcholinesterase compared to FDA-approved acetylcholinesterase inhibitors. The review emphasizes the importance of these compounds in addressing the cholinergic deficits associated with Alzheimer’s disease, where the loss of cholinergic neurons results in reduced acetylcholine levels in the synaptic cleft. Benzimidazole-based thiazole derivatives have demonstrated remarkable inhibitory capabilities against cholinesterase enzymes, with some compounds showing half-maximal inhibitory concentration values as low as 0.10 µM. The review highlights the effectiveness of benzofuran, benzoxazole, indole, indolinone, and coumarin derivatives in inhibiting acetylcholinesterase and providing neuroprotection, making them promising candidates for treating Alzheimer’s disease. Additionally, the review emphasizes the necessity for further research into the mechanisms of action of these substances and their effects on cognitive performance in clinical settings to enhance the quality of life for Alzheimer’s patients. Overall, this work contributes to the ongoing search for effective treatments for Alzheimer’s, stressing the importance of discovering new chemical entities capable of improving neurotransmission and cognitive function.