Molecular Mechanism and Structure-activity Relationship of the Inhibition Effect between Monoamine Oxidase and Selegiline Analogues.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL Current computer-aided drug design Pub Date : 2024-01-01 DOI:10.2174/1573409919666230503143055

Chuanxi Yang, Xiaoning Wang, Chang Gao, Yunxiang Liu, Ziyi Ma, Jinqiu Zang, Haoce Wang, Lin Liu, Yonglin Liu, Haofen Sun, Weiliang Wang

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Abstract

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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来源期刊

Current computer-aided drug design 医学-计算机：跨学科应用

CiteScore

3.70

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.