Discovery of new natural inhibitors for aldosterone synthase (CYP۱۱B۲) for treating cardiovascular disease

Background: Aldosterone is a main mineralocorticoid steroid hormone responsible for the body's balanceof sodium and potassium ions and blood pressure regulation. The aldosterone biosynthesis pathway ismediated by stimulation of Mineralocorticoids receptors and activation of the aldosterone synthase enzyme(CYP۱۱B۲). Abnormal increases in aldosterone levels cause kidney and heart diseases such as increasedblood volume and stimulation of cardiac fibroblasts and cardiac hypertrophy diseases of myocardial fibrosis,and ventricular arrhythmias. More than ۱۰۰۰ natural compounds were screened to discover a potent naturalinhibitor for aldosterone synthase enzyme (CYP۱۱B۲) which is responsible for cardiovascular diseaseprevention.Methods: Virtual screening based on docking studies was performed using the Glide and Induced fit docking(IFD) program in Maestro ۱۲.۸ (Schrodinger, LLC). More than ۱۰۰۰ natural compounds were downloadedfrom the Zinc database and prepared with Ligprep software. Protein was obtained from the protein database(PDB ID: ۴FDH) and prepared using protein preparation software. QSAR and Qikprop studies also wereperformed to evaluate the IC۵۰ and Lipinski data for the selected compounds.Results: The results of molecular binding in XP and IFD studies determined the Nu.۱ ligand (Zinc ID۱۴۶۹۰۰۲۶) with a docking score -۱۲.۴۶۹ kcal/mol, IFD score -۱۰۳۰.۴۷ kcal/mol and calculated IC۵۰ ۸.۲۲۳μM as a potent inhibitory compound for CYP۱۱B۲ enzyme. The HB۶۰ with CID: ۱۰۲۶۳۰۸۲ was consideredas a native ligand with a docking score of -۶.۵۹ Kcal/mol and an IFD score of -۱۰۱۱.۴۴ Kcal/mol andCalculated an IC۵۰ ۷.۹۲ μM with the enzyme.Conclusion: According to the mentioned data Ligand with Zinc ID ۱۴۶۹۰۰۲۶ was selected as a potent naturalinhibitor for the CYP۱۱B۲ receptor compared to the native ligand. This natural ligand helps balance bloodpressure by inhibiting the aldosterone biosynthesis pathway and preventing cardiovascular diseases.