Curcumin Derivatives as Potential c-Src Kinase Inhibitors: Insights from Molecular Docking and Dynamics Simulation

Curcumin, a natural polyphenol derived from turmeric, exhibits significant anticancer properties by targeting various signaling pathways, including c-Src kinase-a crucial mediator of tumor growth and metastasis. Despite its therapeutic promise, curcumin's bioavailability challenges have prompted the design of derivatives to enhance efficacy. This work explores the binding affinity and stability of new curcumin derivatives - (3E,5E)-3,5-bis((3-(2/3/4-substitutedphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)piperidin-4-one (Hpip01-25) acting as c-Src kinase inhibitors through molecular docking and molecular dynamics (MD) simulations. The docking studies showed significant interactions between the derivatives and the active site of c-Src kinase, where Hpip01 had the best docking score (-9.08913 kcal/mol). MD simulations also corroborated the stability of ligand-protein complexes, where Hpip01 had an RMSD very low and strong binding interactions. These results encourage further investigation into the potential of curcumin derivatives as effective inhibitors of c-Src kinase toward selective anticancer therapeutic development. Future work will focus on optimizing these derivatives and experimentally validating their efficacy.