فهرست نشریات علمی دسترسی آزاد ایران

An established target for anticoagulant treatment, factor Xa (FXa) is an essential serine protease in the coagulation cascade.  The search for natural alternatives with safer profiles is prompted by the fact that, despite their clinical efficacy, synthetic inhibitors like rivaroxaban are still burdened by bleeding risks, metabolic interactions, and costs. This study investigated the potential of bioactive compounds from licorice root (Glycyrrhiza glabra L.) as inhibitors of coagulation factor Xa (FXa), a key therapeutic target. Initial in vitro screening of isoliquiritigenin, glycyrrhizic acid, and glabridin identified isoliquiritigenin as the sole compound exhibiting inhibitory activity. Therefore, an integrated in vitro and in silico evaluation of isoliquiritigenin was conducted, utilizing rivaroxaban as a reference inhibitor. In conclusion, the findings identify isoliquiritigenin as a promising natural scaffold for FXa inhibition, warranting further investigation. Frontier molecular orbital (FMO) analysis, molecular electrostatic potential (MEP), non-covalent interaction (NCI) mapping, molecular docking, molecular dynamics (MD) simulations, and ADMET/toxicity predictions were among the computational techniques used. The results indicated that isoliquiritigenin inhibited the activity of FXa dose-dependent manner. Although rivaroxaban demonstrated higher electronic stability and complementarity, the FMO and MEP results showed that isoliquiritigenin has reactive sites for hydrogen bonding. Both ligands interact with the catalytic residues of FXa, according to docking, but rivaroxaban has a higher binding affinity. While isoliquiritigenin exhibited more flexibility while maintaining compactness, MD simulations verified that rivaroxaban maintained higher structural stability. According to toxicity predictions, isoliquiritigenin had a lower carcinogenic potential than rivaroxaban, but it was more likely to be ecotoxic and mutagenic. In conclusion, isoliquiritigenin was identified as a weak inhibitor of FXa and represents a potential natural scaffold for the design of more potent derivatives. However, its low intrinsic potency (IC₅₀ ~700 µM) represents a major limitation, necessitating significant structural optimization to achieve therapeutic relevance. Isoliquiritigenin may have a pharmacological significance and could be utilized as a lead compound for more potent FXa inhibitors, although its stability and safety need to be improved through structural optimization and experimental validation.