Exploring potential inhibitors for colorectal cancer targeting aldehyde dehydrogenase X (ALDH1B1) using molecular docking
Keywords:
Colorectal cancer, ALDH1B1, molecular docking, bioactive compounds, molecular mechanismsAbstract
Background: Colorectal cancer (CRC) is a major global health concern, demanding continuous exploration of novel therapeutic avenues. Aldehyde dehydrogenase X (ALDH1B1) has surfaced as a promising CRC target due to its involvement in cancer progression and resistance to conventional treatments. This study integrates insights from scientific literature, incorporating prevalence data, current treatments, highlighting the need for innovative therapeutic strategies.
Methods: Facing challenges in efficacy and side effects, a paradigm shift towards targeted therapies is crucial for CRC. Molecular docking, a robust computational tool, systematically identifies potential inhibitors by simulating ligand-protein interactions. The study aims to contribute to more effective and targeted therapeutic approaches for CRC by exclusively focusing on ALDH1B1, informed by prevalence data and insights from the current treatment landscape.
Results: The assessment using molecular docking revealed β-sitosterol as the top affinity ligand among twenty-one compounds targeting ALDH1B1. Validation with the original ligand NAD ensures the computational predictions' reliability. Two-dimensional representations offered insights into ligand-receptor interactions, emphasizing β-sitosterol's dynamic engagement with ALDH1B1 through hydrogen bonds and hydrophobic interactions. The study showcased the interaction between ALDH1B1 and irinotecan, unraveling intricate hydrogen bonds. Three-dimensional visualizations further elucidated complex interactions within the system.
Conclusion: β-sitosterol has anticancer features such as apoptosis induction, cell cycle arrest, anti-angiogenic actions, and anti-inflammatory effects. As an antioxidant, it protects cells from oxidative stress, suggesting CRC treatment potential. Molecular docking suggests CRC ALDH1B1 targeted treatments. Clinical validations, molecular mechanisms, combination therapy, bioactive molecule exploration, and precision medicine should be the emphasis of future research to improve therapeutic outcomes.
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