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2000
Volume 21, Issue 3
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer lacking specific receptors, with dysregulated and overactivated Hedgehog (Hh) and mTOR/PI3K/AKT signaling pathways as potential therapeutic targets.

Objective

This study aimed to identify potential inhibitors among 53 alkaloids derived from 9 marine bryozoans using approaches. It sought to analyze their impact on key signaling targets and their potential for future experimental validation.

Methods

In this research, selected targets were evaluated for protein-protein interactions, co-expression survival, and expression profiles. The protein expression was validated through the Human Protein Atlas (HPA) database and druggability through DGIdb. Online web servers were employed to assess drug-likeness, physiochemical properties, pharmacokinetics, and toxicological characteristics of the compounds. Molecular docking and dynamic simulations were carried out for ligand-protein interactions. Common Pharmacophore features, bioavailability, bioactivity, and biological activity spectrum (BAS) were also analyzed.

Results

Out of the 13 compounds studied, 10 displayed strong binding affinity with binding energies ranging from >-6.5 to <-8 Kcal/mol across all targets. Molecular dynamics simulations provided insights into Amathamide E's stability and conformational changes. Pharmacophore modeling revealed common features in 14 compounds potentially responsible for their biological activity.

Conclusion

Our findings indicate the potential of marine-derived compounds as TNBC inhibitors. Further and validation is necessary to establish their effectiveness and explore their role as novel anti-TNBC agents.

© 2025 Bentham Science Publishers
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Identification of Novel Marine Bioactive Compound as Potential Multiple Inhibitors in Triple-negative Breast Cancer - An in silico Approach
Curr. Computeraided Drug Des. 21, 375 (2025); https://doi.org/10.2174/0115734099287118240102112337
/content/journals/cad/10.2174/0115734099287118240102112337
/content/journals/cad/10.2174/0115734099287118240102112337
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Drug-likeness and physiochemical properties of all 53 compounds. Pharmacokinetics of 53 compounds. Metabolism of alkaloids. Toxicity profiles of the alkaloids. PreADMET of alkaloids. List of alkaloids names, PubChem ID, and 2D structure. Predicted partners of targets from Fpclass. Druggability of the targets. Common pharmacophore feature between 14 compounds. Bioactivity Score of selected ligands from Molinspiration. Compounds & drugs similar to amathaspiramide D. Compounds & drugs similar to aspidostomide A. Compounds & drugs similar to convolutamydine B. Correlation coefficient of target genes from GEPIA. Survival analysis of targets in KM Plotter. The phosphoprotein expression level of targets in normal and tumor. () Bar plot from ShinyGO for Kegg pathway () Breast cancer-related pathway. Bioavailability radar of ligands.

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  • Article Type:     Research Article
Keyword(s): Cancer; docking; marine alkaloids; mortality; receptor; Triple-negative breast cancer (TNBCs)

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