The vitamin K cycle, particularly involving the enzyme VKORC1 (Vitamin K epoxide reductase complex subunit 1), plays a critical role in blood coagulation processes. Any interference with this cycle is often linked to vascular disorders, including myocardial infarction and stroke. Although warfarin is a widely prescribed anticoagulant, it carries risks due to interactions with many other medications, highlighting the need for safer alternatives. The ethanol extract of celery leaves (Apium graveolens L.) demonstrates promising anticoagulant effects, yet the specific active compound remains unidentified. Computer-aided drug design (CADD) techniques enable in silico prediction of compound interactions with target binding sites. This study sought to forecast binding interactions and identify stable complexes formed by compounds from the ethanol extract of celery leaves acting as VKORC1 antagonists. Twenty-three compounds were docked using AutoDock 4.2, followed by molecular dynamics simulation in AMBER 18 to evaluate the stability of the top five candidates. Docking results from 17 tested ligands identified five leading compounds: 6-isopentenyloxy-isobergapten (S1), Heratomin (S2), Apigenin (S3), Lanatin (S4), and Isoimperatorin (S5), with ΔG values of −9.27, −9.26, −9.22, −9.13, and −8.94 kcal/mol, respectively. Subsequent MD simulation over 100 ns confirmed 6-isopentenyloxy-isobergapten as the most effective ligand for maintaining complex stability among the five. In summary, 6-isopentenyloxy-isobergapten derived from celery leaves shows promise as a potential anticoagulant targeting VKORC1.
