Molecular dynamics and experimental evaluation of piperine as a potential mTOR inhibitor in colon cancer cells.

Piperine, a natural alkaloid found in black pepper (), has the chemical formula C₁₇H₁₉NO₃ and a molecular weight of 285.34 g/mol. This research investigated its effect on the mTOR protein, which plays a crucial role in cancer development, using molecular docking, dynamic simulations, MTT, and scratch wound assays on the HCT-116 colon cancer cell line. Molecular docking revealed that piperine exhibited a binding affinity of - 8.3 kcal/mol to the mTOR protein, which is significantly comparable to rapamycin's binding affinity of - 8.8 kcal/mol, a well-known mTOR inhibitor. This comparison highlights that piperine demonstrates a substantial ability to interact with the mTOR binding site, making it a potential candidate for further evaluation. Molecular dynamics simulation studies over 100 ns confirmed that piperine remains stable and firmly bound to the mTOR active site, binding in an ATP-competitive mode. MTT assay results revealed that piperine significantly reduced cancer cell viability, with IC50 values of 84.5 ± 0.5 µM at 24 h, 46.3 ± 0.26 µM at 48 h, and 19.73 ± 0.25 µM at 72 h, while the scratch wound assay confirmed its inhibition of cancer cell migration, suggesting potential to suppress metastasis. These findings indicate that piperine is a promising mTOR inhibitor with potential applications in cancer therapy, though further research is needed.