In Silico Investigation of Xanthone Derivative Potency in Inhibiting Carbonic Anhydrase Ii (Ca Ii) Using Molecular Docking and Molecular Dynamics (Md) Simulation

Abstract

Objective: Hypertension is the leading contributor to all-cause death and disability worldwide. One of the most well-known first-line antihypertensive drugs is chlorthalidone which treats hypertension through carbonic anhydrase (CA) II inhibition. However, due to the high number of cases of hypertension, a more potent medication is still needed. Xanthone is a potential candidate for the compound group for its potency in inhibiting CA II. Therefore, this research aims to evaluate around 500 xanthones’ potency as a better oral antihypertensive drug than chlorthalidone. Methods: 507 xanthones were analyzed for their potency using in silico method. Xanthone’s structures were retrieved from the PubChem website or built using Avogadro software, while the CA II receptor was retrieved from The RCSB website. Then molecular docking, ADME evaluation, and toxicity test were evaluated from selected ligands. Finally, a molecular dynamics simulation was conducted to evaluate the stability of the potential ligand as the inhibitor of CA II protein. Results: This research found that globulixanthone c is considered to be a better CA II inhibitor compared to chlorthalidone. It is due to its lower binding affinity compared to chlorthalidone and its stable binding to CA II’s important inhibition sites with low fluctuation. It also has the potential to be consumed orally because it fulfills all of Lipinski's rule of five standards and its toxicity is on the moderate level. Conclusion: Globulixanthone c, a type of prenylated xanthones group, showed the best potential activity as the inhibitor of CA II protein to treat hypertension among other xanthones.

Molecular Docking Study and Pharmacophore Modelling of Ursolic Acid as an Antimalarial Using Structure-Based Drug Design Method

“…The first step taken was using the protein data bank database (https://www.rcsb.org/) as the source to download the receptors in (.pdb) format [10][11][12][13]. Afterwards, the preparation of each receptor was carried out by separating it from the complexed lead compounds using Discovery Studio Visualizer software.…”