Interactions of Linalool and Linalyl Acetate with Selected Dog Cytochrome P450 (CYP) Proteins Identified by In Silico...

Background: Cytochrome P450 (CYP450) enzymes play a central role in the metabolism of xenobiotics, including plant-derived compounds such as terpenoids. Objectives: This study aimed to predict the molecular interactions of linalool (LIN) and linalyl acetate (LINAct), major constituents of lavender essential oil, with the canine CYP2B11, CYP2C21, and CYP2D15 isoforms, using in silico approaches. Methods: Three-dimensional (3D) models of the target enzymes were generated through homology modeling using SWISS-MODEL and validated based on global model quality estimate (GMQE) and QMEAN Z-score metrics. Ligand structures were optimized in the Molecular Operating Environment (MOE), and pharmacophoric features were analyzed. Molecular docking simulations were performed using AutoDock Vina, followed by visualization of interactions in MOE. Results: LIN and LINAct exhibit favorable binding affinities with all three isoforms, suggesting their potential as substrates or modulators. Hydrogen bonding and hydrophobic interactions were the predominant forces stabilizing the ligand-enzyme complexes. Conclusions: These findings provide a computational basis for understanding the hepatic metabolism of LIN and LINAct in dogs, offering preliminary insights into the role of specific CYP isoforms in their biotransformation.