In:
RSC Medicinal Chemistry, Royal Society of Chemistry (RSC), Vol. 13, No. 8 ( 2022), p. 944-954
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 IC 50 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 of 0.03 mg kg −1 , proving selective BChE inhibition to lead to effective neuroprotectivity in AD.
Type of Medium:
Online Resource
ISSN:
2632-8682
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2022
detail.hit.zdb_id:
3005515-5
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