Current Computer-Aided Drug DesignCurrent Computer-Aided Drug DesignCurrent Computer-Aided Drug Design1573-40991875-6697Bentham Science64410210.2174/1573409919666230503143055ChemistryResearch ArticleMolecular Mechanism and Structure-activity Relationship of the Inhibition Effect between Monoamine Oxidase and Selegiline AnaloguesYangChuanxiinfo@benthamscience.netWangXiaoninginfo@benthamscience.netGaoChanginfo@benthamscience.netLiuYunxianginfo@benthamscience.netMaZiyiinfo@benthamscience.netZangJinqiuinfo@benthamscience.netWangHaoceinfo@benthamscience.netLiuLininfo@benthamscience.netLiuYonglininfo@benthamscience.netSunHaofeninfo@benthamscience.netWangWeilianginfo@benthamscience.netSchool of Environmental and Municipal Engineering, Qingdao University of TechnologySchool of Mechanical Engineering and Automation, Northeastern University, Qingdao Jiaming Measurement and Control Technology Co., Ltd, Environmental Monitoring Station of Yuncheng County Environmental Protection Bureau0105202420547448507012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjeid.com/1573-4099/article/view/644102

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 (IC50) 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.

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