Silalai Patamawadee, Jaipea Suwichada, Tocharus Jiraporn, Athipornchai Anan, Suksamrarn Apichart, Saeeng Rungnapha
Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
ACS Omega. 2022 Jul 6;7(28):24302-24316. doi: 10.1021/acsomega.2c01593. eCollection 2022 Jul 19.
A novel series of 1,2,3-triazole-genipin analogues were designed, synthesized, and evaluated for neuroprotective activity, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitory activity. The genipin analogues bearing bromoethyl- and diphenylhydroxy-triazole showed neuroprotective properties against HO toxicity along with potent inhibitory activity on BuChE with IC values of 31.77 and 54.33 μM, respectively, compared with galantamine (IC = 34.05 μM). The molecular docking studies of these genipin analogues showed good binding energy and interact well with the key amino acids of BuChE hydrogen-bonding and hydrophobic interactions. Triazole genipins might be promising lead compounds as anti-Alzheimer's agents.
设计、合成了一系列新型的1,2,3-三唑-京尼平类似物，并对其神经保护活性、乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制活性进行了评估。带有溴乙基和二苯基羟基三唑的京尼平类似物对HO毒性具有神经保护特性，同时对BuChE具有较强的抑制活性，IC值分别为31.77和54.33 μM，而加兰他敏的IC值为34.05 μM。这些京尼平类似物的分子对接研究显示出良好的结合能，并通过氢键和疏水相互作用与BuChE的关键氨基酸良好地相互作用。三唑京尼平可能是有前景的抗阿尔茨海默病先导化合物。
