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Synthesis, bioactivity and molecular modeling studies on potential anti-Alzheimer piperidinehydrazide-hydrazones.
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2018-11-28 , DOI: 10.1016/j.bioorg.2018.11.051
Sulunay Parlar 1 , Gozde Sayar 1 , Ayse Hande Tarikogullari 1 , Sumru Sozer Karadagli 2 , Vildan Alptuzun 1 , Ercin Erciyas 1 , Ulrike Holzgrabe 3
Affiliation  

A group of N-benzylpiperidine-3/4-carbohydrazide-hydrazones were designed, synthesized and evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, Aβ42 self-aggregation inhibitory potentials, and antioxidant capacities, in vitro. All of the compounds displayed eeAChE and huAChE inhibitory activity in a range of IC50 = 5.68-11.35 µM and IC50 = 8.80-74.40 µM, respectively and most of the compounds exhibited good to moderate inhibitory activity on BuChE enzyme. Kinetic analysis and molecular modeling studies were also performed for the most potent compounds (1g and 1j). Not only the molecular modeling studies but also the kinetic analysis suggested that these compounds might be able to interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of the enzymes. In the light of the results, compound 1g and compound 1j may be suggested as lead compounds for multifunctional therapy of AD.

中文翻译:

潜在的抗阿兹海默哌啶酰肼-的合成,生物活性和分子模型研究。

设计,合成和评估了一组N-苄基哌啶-3 / 4-碳酰肼-az,并在体外进行了乙酰胆碱酯酶(AChE),丁酰胆碱酯酶(BuChE)活性,Aβ42自聚集抑制电位和抗氧化能力的评估。所有这些化合物分别对eeAChE和huAChE表现出抑制活性,分别在IC50 = 5.68-11.35 µM和IC50 = 8.80-74.40 µM范围内,并且大多数化合物对BuChE酶表现出良好至中等的抑制活性。还对最有效的化合物(1g和1j)进行了动力学分析和分子建模研究。不仅是分子建模研究,而且动力学分析还表明这些化合物可能能够与酶的催化活性位点(CAS)和外围阴离子位点(PAS)相互作用。根据结果​​,
更新日期:2018-11-28
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