Computational Insight into Warfarin Blockage by Silymarin Components via DFT and Molecular Docking

Abstract Silymarin has been utilized as a traditional, complementary, and integrative medicine for centuries, despite a poor molecular‐level understanding of its interactions with other medicinal compounds and enzyme structures. However, recent studies indicate that this supplement, as with many others, should be considered with caution because it has the potential to interact with many drugs, medical plants, and foods. Silymarin is composed of several compounds that are either enantiomeric or have similar structures. Thus, this study presents the electronic structure properties and reactivity characteristics of silymarin components and warfarin through density functional theory modeling at the M06‐2X/6–311 + G(d,p) level of theory. The ligand‐protein interactions of the compounds with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) enzymes, and alanine transaminase were presented using molecular docking. The critical residue‐based interactions of silymarin components and warfarin were fingerprinted. Furthermore, their drug‐likeness and toxicity characteristics were compared to those of warfarin and the well‐known flavonoids, taxifolin, and quercetin. The possibility of inhibiting the target enzymes to reduce the effectiveness of warfarin has been highlighted.