9SND

Mus musculus acetylcholinesterase in complex with 2-(1H-indol-3-yl)-N-(2-methoxybenzyl)ethan-1-amine

これはPDB形式変換不可エントリーです。

9SND の概要

• エントリーDOI: 10.2210/pdb9snd/pdb
• 分子名称: Acetylcholinesterase, 2-(1~{H}-indol-3-yl)-~{N}-[(2-methoxyphenyl)methyl]ethanamine, 2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol, ... (6 entities in total)
• 機能のキーワード: reversible, inhibitor, insecticide, hydrolase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 121795.85

構造登録者

Ekstrom, F.,Forsgen, N. (登録日: 2025-09-10, 公開日: 2026-01-28)

主引用文献

Rajeshwari, R.,Duvauchelle, V.,Lindgren, C.,Stangner, K.,Knutsson, S.,Forsgren, N.,Ekstrom, F.,Kamau, L.,Linusson, A.
Potent and selective indole-based inhibitors targeting disease-transmitting mosquitoes.
Rsc Med Chem, 2025

PubMed Abstract: Vector control with insecticides is an important preventive measure against mosquito-borne infectious diseases, such as malaria and dengue. The intensive usage of few insecticides has resulted in emerging resistance in mosquitoes, and unwanted off-target toxic effects. Therefore, there is great interest in alternative active ingredients. Here, we explore indole-based compounds as selective inhibitors against acetylcholinesterase 1 (AChE1) from the disease-transmitting mosquitoes (, AChE1) and (, AChE1) as potential candidates for future insecticides used in vector control. Three sets of compounds were designed to explore their structure-activity relationship, and investigate their potentials regarding potency and selectivity. 26 indole-based compounds were synthesized and biochemically evaluated for inhibition against AChE1, AChE1, and human AChE (AChE). The compounds were shown to be potent inhibitors against AChE1, and selective for AChE1 over AChE. -Methylation of the indole moiety clearly increased the inhibition potency, and a bulkier benzyl moiety improved the selectivity. X-ray crystallography shows that the inhibitors bind at the bottom of the active site gorge of mouse AChE (AChE), while molecular dynamics simulations revealed different binding poses in AChE and AChE1. Four potent and selective inhibitors were subjected to mosquito testing. Topical application showed strong insecticidal effects on and , highlighting this compound class as an interesting alternative for future insecticide research.

PubMed: 41551022
DOI: 10.1039/d5md00797f

実験手法

X-RAY DIFFRACTION (2.4 Å)