Synthesis, Docking and Acetylcholinesterase Inhibitory Evaluation of 1,3,4-Thiadiazole Derivatives as Potential Anti-Alzheimer Agents

Abstract

Background: According to the cholinergic hypothesis for Alzheimer’s disease, potentiation of cholinergic neurotransmission is one of the best strategies for combating dementia. Methods: A new series of benzamide derivatives bearing 1,3,4-thiadiazole nucleus were synthesized and subsequently, their anticholinesterase activity was evaluated. Molecular docking was carried out to explore the likely binding mode and interactions. Results: Fortunately, some of the tested compounds exhibited more activity than donepezil as a reference drug (IC50 = 0.6 ± 0.05 µM). Some of the evaluated derivatives displayed potency in the nanomolar range. Compound 7e with fluorine atom on the meta position of the phenyl ring was the most active compound in this series (IC50 = 1.82 ± 0.6 nM). Conclusion: The 1,3,4-thiadiazole derivatives that were synthesized and tested in the current manuscript demonstrated remarkable anticholinesterase activity. Therefore, these compounds could be suggested as potential anti-Alzheimer agents.

Keywords

• 1
• 3
• 4-thiadiazole
• acetylcholinesterase
• alzheimer disease
• synthesis