1st International and 10th National Iranian Conference on Bioinformatics

Discovery of new natural inhibitors for aldosterone synthase (CYP11B2) for treating cardiovascular disease

Paper ID : 1110-ICB10

Authors:

سینا محمدمهری *¹, مهشاد شهریاری¹, صمد نژادابراهیمی²

¹پژوهشکده گیاهان و مواد اولیه داروئی دانشگاه شهیدبهشتی تهران

²عضو هیئت علمی رشته فیتوشیمی پژوهشکده گیاهان و مواد اولیه دارویی دانشگاه شهیدبهشتی تهران

Abstract:

Background: Aldosterone is a main mineralocorticoid steroid hormone responsible for the body's balance of sodium and potassium ions and blood pressure regulation [1]. The aldosterone biosynthesis pathway is mediated by stimulation of Mineralocorticoids receptors and activation of the aldosterone synthase enzyme (CYP11B2) [2]. Abnormal increases in aldosterone levels cause kidney and heart diseases such as increased blood volume and stimulation of cardiac fibroblasts and cardiac hypertrophy diseases of myocardial fibrosis, and ventricular arrhythmias. More than 1000 natural compounds were screened to discover a potent natural inhibitor for aldosterone synthase enzyme (CYP11B2) which is responsible for cardiovascular disease prevention.
Methods: Virtual screening based on docking studies was performed using the Glide and Induced fit docking (IFD) program in Maestro 12.8 (Schrodinger, LLC). More than 1000 natural compounds were downloaded from the Zinc database and prepared with Ligprep software. Protein was obtained from the protein database (PDB ID: 4FDH) and prepared using protein preparation software. QSAR and Qikprop studies also were performed to evaluate the IC50 and Lipinski data for the selected compounds.
Results: The results of molecular binding in XP and IFD studies determined the Nu.1 ligand (Zinc ID 14690026) with a docking score -12.469 kcal/mol, IFD score -1030.47 kcal/mol and calculated IC50 8.223 µM as a potent inhibitory compound for CYP11B2 enzyme. The HB60 with CID: 10263082 was considered as a native ligand with a docking score of -6.59 Kcal/mol and an IFD score of -1011.44 Kcal/mol and Calculated an IC50 7.92 µM with the enzyme.
Conclusion: According to the mentioned data Ligand with Zinc ID 14690026 was selected as a potent natural inhibitor for the CYP11B2 receptor compared to the native ligand. This natural ligand helps balance blood pressure by inhibiting the aldosterone biosynthesis pathway and preventing cardiovascular diseases.

Keywords:

Aldosterone synthase, CYP11B2 enzyme, Cardiac hypertrophy, Blood pressure diseases

Status : Paper Accepted (Poster Presentation)