In Silico molecular docking evaluation of mangiferin against key colorectal cancer associated proteins
Paper Details
In Silico molecular docking evaluation of mangiferin against key colorectal cancer associated proteins
Abstract
Colorectal cancer (CRC) is a multifactorial malignancy driven by dysregulated inflammatory signaling, aberrant cell proliferation, defective apoptosis, loss of tumor suppressor functions, and aberrant activation of oncogenic signaling pathways. The identification of multi-target agents capable of simultaneously modulating these interconnected pathways represents a promising therapeutic strategy. In the present study, the multi-target therapeutic potential of mangiferin, a bioactive C-glucosyl xanthone, was systematically evaluated against key CRC-associated molecular targets using structure-based molecular docking. Molecular docking was performed using AutoDock Vina against proteins involved in inflammation (TNF-α and COX-2), proliferation and angiogenesis (K-Ras, BRAF, β-catenin, VEGFR-2, and Cyclin D1), apoptosis (Bcl-2, BAX, and Caspase-3), tumor suppression (p53 and APC), and the PI3K/Akt/mTOR signaling pathway (PI3K-α, AKT, and mTOR). Protein structures were retrieved from the RCSB Protein Data Bank and docked following binding-site prediction using CASTp. Mangiferin exhibited strong to moderate binding affinities toward all selected targets, with docking scores ranging from −10.5 to −7.0 kcal/mol. The strongest binding affinity was observed with TNF-α (−10.5 kcal/mol), followed by AKT (−10.3 kcal/mol), COX-2 (−9.8 kcal/mol), BRAF (−9.4 kcal/mol), and PI3K-α (−9.4 kcal/mol), indicating effective targeting of inflammatory mediators and oncogenic survival signaling pathways. Moderate binding affinities were observed for VEGFR-2 and p53 (−8.5 kcal/mol), K-Ras and APC (−8.4 kcal/mol), and Bcl-2 (−8.2 kcal/mol), suggesting potential inhibition of angiogenesis, cell proliferation, and anti-apoptotic signaling. Additionally, mangiferin demonstrated favorable interactions with β-catenin (−7.7 kcal/mol), caspase-3 (−7.6 kcal/mol), mTOR (−7.5 kcal/mol), BAX (−7.1 kcal/mol), and Cyclin D1 (−7.0 kcal/mol), highlighting its capacity to modulate Wnt signaling, apoptosis, cell-cycle regulation, and PI3K/AKT/mTOR pathway components. Overall, mangiferin–protein complexes were stabilized through a combination of hydrogen bonding and hydrophobic π-interactions, supporting mangiferin as a promising multi-target phytochemical with therapeutic relevance in colorectal cancer.
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Monisha Ravi, A. Malarvizhi*, 2026. In Silico molecular docking evaluation of mangiferin against key colorectal cancer associated proteins. Int. J. Biosci., 28(3), 22-32.
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