Scholarlink

<p>Melanoma, a type of skin cancer, fifth leading cause of cancer-related mortality due to its propensity to metastasize from the skin to other organs, largely driven by the constitutive activation of the PI3K/AKT signaling axis. This study aimed to investigate the inhibitory mechanisms and biological pathways of Arbutin (ArB) in melanoma. ArB, a bioactive compound, and its targets were identified from CTD, PharmMapper, Swiss Target Prediction, and ETCM. Similarly, disease-related targets were obtained using GeneCards, GEO, and the CTD database. A Venn diagram showed overlapping targets between the two groups. GO, KEGG enrichment analysis, and PPI networks were adopted to identify potential core targets associated with ArB and melanoma. Stability and affinity were evaluated using molecular docking, 100 ns molecular dynamics (MD) simulation, principal component analysis (PCA), free energy landscape (FEL), and density functional theory (DFT) analyses. AKT1 emerged as a key gene with strong binding to ArB, exhibiting an affinity of -7.9&#xa0;kcal/mol as determined by molecular docking. MMGBSA and MMPBSA ΔTotal energies of -37.17 and − 22.15&#xa0;kcal/mol, respectively, further supported the effective binding affinity. Furthermore, DFT calculations determined a HOMO-LUMO energy gap of 5.72&#xa0;eV, confirming the molecule’s kinetic stability and favorable electronic reactivity. ADMET analysis confirmed a safety profile but can induce nephrotoxicity, which should be evaluated in vivo. We explored ArB as a potential AKT1 inhibitor and propose that it could serve as a lead compound for the development of targeted melanoma treatments.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Exploring the Molecular Mechanism of Arbutin as a Potential Inhibitor Against Melanoma: Insights from Network Pharmacology, Molecular Docking, Dynamics Simulations, and DFT Analysis

  • 期刊论文

  • 发表日期：

    2026年4月21日

查看全文
  • Md Rashedul Islam,
  • Ishtiaq Qadri,
  • Muhammad Afzal,
  • Misbahuddin Rafeeq,
  • Abdullah Alfaifi,
  • Khadijah Abdullah Alfaifi,
  • Sami I. Alzarea,
  • Ehab M. M. Ali,
  • Imran Kazmi

摘要

Melanoma, a type of skin cancer, fifth leading cause of cancer-related mortality due to its propensity to metastasize from the skin to other organs, largely driven by the constitutive activation of the PI3K/AKT signaling axis. This study aimed to investigate the inhibitory mechanisms and biological pathways of Arbutin (ArB) in melanoma. ArB, a bioactive compound, and its targets were identified from CTD, PharmMapper, Swiss Target Prediction, and ETCM. Similarly, disease-related targets were obtained using GeneCards, GEO, and the CTD database. A Venn diagram showed overlapping targets between the two groups. GO, KEGG enrichment analysis, and PPI networks were adopted to identify potential core targets associated with ArB and melanoma. Stability and affinity were evaluated using molecular docking, 100 ns molecular dynamics (MD) simulation, principal component analysis (PCA), free energy landscape (FEL), and density functional theory (DFT) analyses. AKT1 emerged as a key gene with strong binding to ArB, exhibiting an affinity of -7.9 kcal/mol as determined by molecular docking. MMGBSA and MMPBSA ΔTotal energies of -37.17 and − 22.15 kcal/mol, respectively, further supported the effective binding affinity. Furthermore, DFT calculations determined a HOMO-LUMO energy gap of 5.72 eV, confirming the molecule’s kinetic stability and favorable electronic reactivity. ADMET analysis confirmed a safety profile but can induce nephrotoxicity, which should be evaluated in vivo. We explored ArB as a potential AKT1 inhibitor and propose that it could serve as a lead compound for the development of targeted melanoma treatments.