Integrated in vivo and in silico ADMET and metabolomic profiling of basil seed bioactives Methyl eugenol and linalool.

Abstract

Biotransformation pathways critically predict rational drug design by elucidating a compound's absorption, distribution, metabolism, excretion and toxicity (ADMET) profile. This investigation provides a consolidated in vivo and in silico assessment of methyl eugenol (ME) and linalool (LL). Acute oral toxicity studies in Swiss albino rats revealed no mortality or clinical distress up to 2000 mg/kg. Noncompartmental pharmacokinetic analysis showed both compounds reached maximum plasma concentration at 4 hr (413.20 ng/mL for ME; 248.66 ng/mL for LL) and were largely cleared within 24 hrs. Despite identical T_max values, their elimination half-lives differed significantly (30.0 h for ME vs. 117.5 h for LL), leading to greater systemic exposure for LL. Time-resolved LC-MS/MS identified distinct phase I metabolic pathways for each compound, which were corroborated by in silico predictions. Molecular docking against α-amylase and acetylcholinesterase, indicated favorable binding energies for both compounds, with ME showing slightly stronger affinity in some instances (e.g., -5.6 vs. -5.0 kcal/mol for α-amylase). However, LL consistently exhibited lower RMSD values, suggesting more specific binding. This integrated empirical-computational approach offers a foundational ADMET profile, guiding future structural modifications to optimize their therapeutic potential.