Discovery of MMP1 Inhibitors from Dandelion using Molecular Simulation and Bioactivity Test.

IF 2.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Current topics in medicinal chemistry Pub Date : 2025-05-12 DOI:10.2174/0115680266387669250509094221

Yaxuan Huang, Dewen Jiang, Liqin Zhang, Yonghao Zhang, Mingkai Wu, Xiaojie Jin, Jianjun Luo, Dabo Pan

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引用次数: 0

Abstract

Background: MMP1 (matrix metallopeptidase 1) plays a significant role in the degradation of collagen fibres within the extracellular matrix, and has been linked to a multitude of biological processes, including rheumatoid arthritis, osteoarthritis, periodontal disease, and tumor invasion.

Objective: In order to discover inhibitors of MMP1 that originate from the phytochemicals of the dandelion (Taraxacum mongolicum Hand.-Mazz.).

Methods: The herbal constituents of the dandelion were retrieved from the HERB database. A multifaceted approach including molecular docking, MMP1 enzyme assays, and molecular dynamics simulations was used to identify potential MMP1 inhibitors among the chemical compounds present in the dandelion.

Results: A total of 61 chemical constituents of the dandelion were collated from the HERB database. A potential MMP1 inhibitor was identified through a combination of molecular docking and an MMP1 enzyme bioactivity assay. Cichoric acid demonstrated pronounced inhibitory activity against MMP1, with an IC50 value of 7.81 ± 2.60 µM. Molecular dynamics simulations and binding free energy calculations indicated that the nonpolar interaction energies of LEU181, ARG214, VAL215, HIS218, GLU219, HIS228, PRO238, and SER239 played a primary role in the binding of cichoric acid to MMP1.

Conclusion: The integration of molecular modeling and bioactivity testing proved an effective method for the rapid discovery of targeted small molecule inhibitors. Cichoric acid demonstrated potent MMP1 inhibitory activity and thus represented a promising candidate for further development.

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蒲公英中MMP1抑制剂的分子模拟和生物活性试验

背景：MMP1（基质金属肽酶1）在细胞外基质内胶原纤维的降解中起重要作用，并与多种生物过程有关，包括类风湿关节炎、骨关节炎、牙周病和肿瘤侵袭。目的：从蒲公英（Taraxacum mongolicum Hand.-Mazz.）植物化学物质中寻找MMP1的抑制剂。方法：从中药数据库中检索蒲公英的草药成分。通过分子对接、MMP1酶测定和分子动力学模拟等多方面的方法，研究人员在蒲公英中发现了潜在的MMP1抑制剂。结果：从草本植物数据库中共检出蒲公英61种化学成分。通过分子对接和MMP1酶生物活性测定相结合，确定了一种潜在的MMP1抑制剂。Cichoric acid对MMP1具有明显的抑制作用，IC50值为7.81±2.60µM。分子动力学模拟和结合自由能计算表明，LEU181、ARG214、VAL215、HIS218、GLU219、HIS228、PRO238和SER239的非极性相互作用能在马尾酸与MMP1的结合中起主要作用。结论：分子模拟与生物活性检测相结合是快速发现靶向小分子抑制剂的有效方法。Cichoric acid显示出强大的MMP1抑制活性，因此代表了一个有希望进一步开发的候选物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current topics in medicinal chemistry 医学-医药化学

CiteScore

6.40

自引率

2.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.