Network pharmacology, molecular docking, and molecular dynamics simulation analysis reveal the molecular mechanism of halociline against gastric cancer

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-03-19 DOI:10.1007/s11030-024-10822-y

Xiangru Zha, Rong Ji, Yang Li, Rong Cao, Songlin Zhou

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Abstract

Halociline, a derivative of alkaloids, was isolated from the marine fungus Penicillium griseofulvum by our group. This remarkable compound exhibits promising antineoplastic activity, yet the precise molecular mechanisms underlying its anticancer properties remain enigmatic. To unravel these mechanisms, we employed an integrated approach of network pharmacology analysis, molecular docking simulations, and molecular dynamics simulations to explore halociline therapeutic targets for gastric cancer. The data from network pharmacology indicate that halociline targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells, potentially mediated by diverse pathways including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance. Notably, molecular docking and dynamics simulations revealed a high affinity between halociline and these targets, with free binding energies (ΔE_total) of − 20.28, − 27.94, and − 25.97 kcal/mol for MAPK1, MMP-9, and PIK3CA, respectively. This study offers valuable insights into the potential molecular mechanism of halociline’s inhibition of gastric cancer cells and serves as a valuable reference for future basic research efforts.

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网络药理学、分子对接和分子动力学模拟分析揭示卤西林抗胃癌的分子机制

我们的研究小组从海洋真菌青霉中分离出了一种生物碱衍生物--卤西林。这种非凡的化合物具有良好的抗肿瘤活性，但其抗癌特性的确切分子机制仍是一个谜。为了揭示这些机制，我们采用了网络药理学分析、分子对接模拟和分子动力学模拟等综合方法来探索哈洛西林治疗胃癌的靶点。网络药理学数据表明，哈洛西林靶向胃癌细胞中的MAPK1、MMP-9和PIK3CA，可能由癌症、脂质代谢、动脉粥样硬化和表皮生长因子受体酪氨酸激酶抑制剂耐药等多种途径介导。值得注意的是，分子对接和动力学模拟揭示了卤西林与这些靶点之间的高亲和力，与MAPK1、MMP-9和PIK3CA的自由结合能（ΔEtotal）分别为- 20.28、- 27.94和- 25.97 kcal/mol。这项研究为了解哈洛西林抑制胃癌细胞的潜在分子机制提供了宝贵的见解，为今后的基础研究工作提供了有价值的参考。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;