Computational Assessment of Phytochemical Inhibitors of Cytochrome P450 2E1 (CYP2E1) Implicated in Hepatotoxicity: Comparative Molecular Docking and Interaction Analysis Using Silymarin as a Benchmark
Abstract
Abstract Liver diseases remain a major global health challenge, often driven by oxidative stress and reactive metabolites generated during xenobiotic metabolism. Cytochrome P450 2E1 (CYP2E1) plays a central role in hepatotoxicity through the bioactivation of toxic compounds and excessive production of reactive oxygen species. This study aimed to evaluate the inhibitory potential of selected phytochemicals (curcumin, quercetin, and kaempferol) against CYP2E1 using molecular docking, with silymarin as a benchmark compound. Molecular docking was performed using SwissDock, while UCSF Chimera was used for three-dimensional visualization and interaction confirmation. BIOVIA Discovery Studio Visualizer was employed for detailed 2D interaction profiling, including hydrogen bonding and hydrophobic interaction analysis. Binding affinities were evaluated based on estimated free energy values (ΔG), and interaction patterns were analyzed to assess ligand stability within the CYP2E1 active site. Results revealed that curcumin exhibited the strongest binding affinity (− 6.9889 kcal/mol), outperforming the benchmark ligand silymarin (− 6.5559 kcal/mol), followed by kaempferol (− 6.3145 kcal/mol) and quercetin (− 6.0048 kcal/mol). Curcumin also formed the highest number of hydrogen bonds and demonstrated favorable hydrophobic and short-range interactions within the active site. These combined interactions suggest strong ligand–enzyme stability and effective binding within the CYP2E1…
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Evidence Hub reads this as a preprint, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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