Novel benzimidazole-based pseudo-irreversible butyrylcholinesterase inhibitors with neuroprotective activity in an Alzheimer's disease mouse model.

ABSTRACT: As levels of acetylcholinesterase (AChE) decrease while levels of butyrylcholinesterase (BChE) increase in later stages of Alzheimer's disease (AD), BChE stands out as a promising target for treatment of AD. Therefore, several benzimidazole-carbamates were designed based on docking studies to inhibit BChE selectively over AChE, while retaining a reasonable solubility. Synthesized molecules exhibit IC₅₀ values from 2.4 μM down to 3.7 nM with an overall highly hBChE-selective profile of the designed compound class. After evaluation of potential neurotoxicity, the most promising compound was further investigated in vivo. Compound 11d attenuates Aβ_25-35-induced learning impairments in both spontaneous alternation and passive avoidance responses at a very low dosage

SUBMITTER: Spatz P 

PROVIDER: S-EPMC9384809 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature