单胺氧化酶抑制作用的分子机制及塞来昔布类似物的构效关系。
Molecular Mechanism and Structure-activity Relationship of the Inhibition Effect between Monoamine Oxidase and Selegiline Analogues.
机构信息
School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao, Shandong, 266520, China.
School of Mechanical Engineering and Automation, Northeastern University, Shenyang, Liaoning, 110819, China.
出版信息
Curr Comput Aided Drug Des. 2024;20(5):474-485. doi: 10.2174/1573409919666230503143055.
INTRODUCTION
To investigate the inhibition properties and structure-activity relationship between monoamine oxidase (MAO) and selected monoamine oxidase inhibitors (MAOIs, including selegiline, rasagiline and clorgiline).
METHODS
The inhibition effect and molecular mechanism between MAO and MAOIs were identified via the half maximal inhibitory concentration (IC) and molecular docking technology.
RESULTS
It was indicated that selegiline and rasagiline were MAO B inhibitors, but clorgiline was MAO-A inhibitor based on the selectivity index (SI) of MAOIs (0.000264, 0.0197 and 14607.143 for selegiline, rasagiline and clorgiline, respectively). The high-frequency amino acid residues of the MAOIs and MAO were Ser24, Arg51, Tyr69 and Tyr407 for MAO-A and Arg42 and Tyr435 for MAO B. The MAOIs and MAO A/B pharmacophores included the aromatic core, hydrogen bond acceptor, hydrogen bond donor-acceptor and hydrophobic core.
CONCLUSION
This study shows the inhibition effect and molecular mechanism between MAO and MAOIs and provides valuable findings on the design and treatment of Alzheimer's and Parkinson's diseases.
简介
本研究旨在探究单胺氧化酶（MAO）与所选单胺氧化酶抑制剂（MAOIs，包括司来吉兰、雷沙吉兰和氯吉兰）之间的抑制特性和构效关系。
方法
通过半数最大抑制浓度（IC）和分子对接技术，鉴定 MAO 与 MAOIs 之间的抑制作用和分子机制。
结果
根据 MAOIs 的选择性指数（SI）（司来吉兰、雷沙吉兰和氯吉兰分别为 0.000264、0.0197 和 14607.143），表明司来吉兰和雷沙吉兰为 MAO-B 抑制剂，而氯吉兰为 MAO-A 抑制剂。MAOIs 和 MAO 的高频氨基酸残基分别为 MAO-A 中的 Ser24、Arg51、Tyr69 和 Tyr407 以及 MAO-B 中的 Arg42 和 Tyr435。MAOIs 和 MAO 的药效团包括芳香核、氢键受体、氢键供体-受体和疏水核。
结论
本研究展示了 MAO 与 MAOIs 之间的抑制作用和分子机制，为阿尔茨海默病和帕金森病的设计和治疗提供了有价值的发现。
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