Pharmacophore-Based Discovery of Licoisoflavanone as a Dual CXCR4/CXCR7 Inhibitor for Coronary Artery Disease: Integration of Traditional Chinese Medicine and Modern Computational Approaches

Coronary artery disease (CAD) is still a primary cause of death worldwide, prompting the development of innovative therapeutic strategies. In this work, 149 possible candidates were identified by creating a ligand-based pharmacophore model of traditional Chinese herbal medicines using FDA-approved CAD drugs as templates. Licoisoflavanone (MOL004885) was identified as the most promising dual inhibitor by subsequent molecular docking against the chemokine receptors CXCR4 and CXCR7. It showed significant binding affinities of −10.1 kcal/mol and −9.5 kcal/mol, respectively. Licoisoflavanone’s stability inside the binding sites of both receptors was validated by molecular dynamics simulations conducted over 200 ns, and MMGBSA analysis revealed a particularly advantageous interaction with CXCR4. Stereoisomeric analysis of the [Formula: see text]- and [Formula: see text]-forms of Licoisoflavanone revealed comparable stability and interaction patterns with both receptors. Pharmacokinetic predictions demonstrated nonmutagenic properties and good oral absorption. Additionally, the chemical stability and reactivity balance of the molecule were confirmed using density functional theory (DFT) calculations. These findings further support the dual-targeting potential of both enantiomers. All of these results point to Licoisoflavanone as a good candidate for additional research and development as a novel therapeutic drug that targets CXCR4/CXCR7 in the treatment of CAD.