Structure-Based Molecular Docking of Vitex negundo Phytoconstituents Targeting ACE and HMG-CoA Reductase: Implications for Dual Cardiovascular Therapy

Abstract

The development of multi-target treatment approaches is necessary since cardiovascular illnesses continue to be a major cause of death worldwide. Using a molecular docking technique, the current work assesses the dual inhibitory ability of Vitex negundo phytoconstituents against angiotensin-converting enzyme (ACE) and HMG-CoA reductase (HMGCR). AutoDock Vina was used to perform docking analysis on the crystal structures of ACE (PDB ID: 1O86) and HMGCR (PDB ID: 1DQ8). For comparative analysis, common medications such as lisinopril, captopril, enalaprilat, atorvastatin, simvastatin, and rosuvastatin were utilized. Ursolic acid showed the most dual-target potential among the phytoconstituents, with the highest binding affinity for both targets (up to −10.5 kcal/mol). Vitexin and isovitexin showed significant binding affinities for ACE, while negundoside and casticin showed comparatively larger affinities among the phytocompounds for HMG-CoA reductase. Stable binding via hydrophobic and hydrogen bonding interactions within the active sites was found by the interaction analysis. Overall, the results indicate that the phytoconstituents of Vitex negundo have promising multi-target action related to the treatment of cardiovascular disease. To verify their therapeutic potential, however, more validation via molecular dynamics simulations and experimental research is needed.