Harnessing the synergistic potential of EGCG and camptothecin against skin melanoma: a computational and experimental approach.

IF 3.8 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2025-07-20 DOI:10.1007/s11030-025-11296-2

Ansari Vikhar Danish Ahmad, Qazi Yasar, Syed Ayaz Ali, Subur W Khan, Mohd Mukhtar Khan

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引用次数: 0

Abstract

Skin melanoma remains a major global health concern, necessitating novel therapeutic strategies. Epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, possesses potent antioxidant and anti-inflammatory properties that may suppress melanoma progression. Camptothecin (CPT), a topoisomerase I inhibitor, disrupts DNA replication in cancer cells, demonstrating promise in targeted melanoma therapy. This study employs a comprehensive integrative approach that combines network pharmacology (NP), molecular docking, molecular dynamics (MD) simulations, and in vitro experiments to investigate the potential synergistic anti-melanoma effects of EGCG and CPT. Network pharmacology analysis revealed a complex interaction network comprising 138 nodes and 145 edges, identifying key targets involved in melanoma pathophysiology. KEGG pathway enrichment analysis revealed significant involvement of the PI3K‒Akt signaling pathway in melanoma modulation. Molecular docking studies demonstrated strong binding affinities of camptothecin with EGFR (PDB: 3LZB), with binding energies ranging from - 8.6 to - 10.1 kcal/mol. Molecular dynamics simulations further confirmed the stability of these interactions, with minimal fluctuations observed. Experimental validation via the SRB assay in B16-F10 melanoma cells revealed potent inhibition of cell viability, particularly when EGCG and camptothecin were used in combination, indicating a potential synergistic effect. The observed synergism between EGCG and camptothecin suggests a multitargeted therapeutic approach, leveraging EGCG's antioxidant and anti-inflammatory effects alongside camptothecin's ability to inhibit DNA replication to enhance melanoma suppression. This integrative study highlights the promise of combination therapy using natural and chemotherapeutic agents, paving the way for the development of effective, targeted anticancer treatments for skin melanoma.

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利用EGCG和喜树碱对抗皮肤黑色素瘤的协同潜力：一种计算和实验方法。

皮肤黑色素瘤仍然是一个主要的全球健康问题，需要新的治疗策略。表没食子儿茶素没食子酸酯（EGCG）是绿茶中主要的多酚，具有有效的抗氧化和抗炎特性，可能抑制黑色素瘤的进展。喜树碱（CPT）是一种拓扑异构酶I抑制剂，可破坏癌细胞中的DNA复制，在靶向黑色素瘤治疗中显示出前景。本研究采用网络药理学（NP）、分子对接、分子动力学（MD）模拟和体外实验相结合的综合方法，研究EGCG和CPT潜在的协同抗黑色素瘤作用。网络药理学分析揭示了一个由138个节点和145个边缘组成的复杂相互作用网络，确定了参与黑色素瘤病理生理的关键靶点。KEGG通路富集分析显示PI3K-Akt信号通路显著参与黑色素瘤的调节。分子对接研究表明喜树碱与EGFR具有较强的结合亲和力（PDB: 3LZB），结合能范围为- 8.6 ~ - 10.1 kcal/mol。分子动力学模拟进一步证实了这些相互作用的稳定性，观察到的波动最小。在B16-F10黑色素瘤细胞中进行的SRB实验验证显示，EGCG和喜树碱联合使用对细胞活力有明显的抑制作用，这表明EGCG和喜树碱具有潜在的协同作用。观察到的EGCG和喜树碱之间的协同作用提示了一种多靶向治疗方法，利用EGCG的抗氧化和抗炎作用以及喜树碱抑制DNA复制的能力来增强对黑色素瘤的抑制。这项综合研究强调了使用天然药物和化疗药物联合治疗的前景，为开发有效的、靶向的皮肤黑色素瘤抗癌治疗铺平了道路。

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

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;