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Identification of Novel Marine Bioactive Compound as Potential Multiple Inhibitors in Triple-negative Breast Cancer -
Hema Priya Manivannan1, Vishnu Priya Veeraraghavan1, Arul Prakash Francis1
1Centre of Molecular Medicine and Diagnostics (COMManD), Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai-600077, India.
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 in silico 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, coexpression 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 in vitro and in vivo validation is necessary to establish their effectiveness and explore their role as novel anti-TNBC agents.
Insights
Marine bryozoan alkaloids show promise as triple-negative breast cancer (TNBC) inhibitors. Computational analysis identified compounds with strong binding affinities, suggesting potential for novel anti-TNBC drug development.
Area of Science:
- Marine natural products chemistry
- Computational drug discovery
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
- Dysregulated Hedgehog (Hh) and mTOR/PI3K/AKT pathways are implicated in TNBC progression.
- Marine bryozoans are a source of diverse bioactive alkaloids.
Purpose of the Study:
- To identify potential TNBC inhibitors from marine bryozoan alkaloids using in silico methods.
- To evaluate the impact of these compounds on key signaling pathways.
- To assess their suitability for further experimental validation.
Main Methods:
- In silico screening of 53 alkaloids against TNBC targets.
- Analysis of protein-protein interactions, coexpression, and expression profiles.
- Molecular docking, dynamic simulations, and pharmacophore modeling.
- Assessment of drug-likeness, pharmacokinetics, and toxicity using web servers.
Main Results:
- Ten out of thirteen evaluated compounds exhibited strong binding affinities (>-6.5 to <-8 Kcal/mol).
- Molecular dynamics simulations revealed the stability of Amathamide E.
- Pharmacophore modeling identified common features in 14 compounds linked to biological activity.
Conclusions:
- Marine-derived alkaloids show potential as novel inhibitors for triple-negative breast cancer.
- Further in vitro and in vivo studies are required to confirm efficacy.
- These compounds represent promising candidates for developing new anti-TNBC agents.
