Molecular Docking, Pharmacological Profiling, and Molecular Dynamics Simulation of Potential Antihyperuricemic Agent from Secondary Metabolites of Dillenia philippinensis Rolfe (Dilleniaceae)

Crystal accumulation in the joints due to increased serum uric acid (sUA) may lead to an inflammatory condition called gout. Increased sUA is caused by the excessive reabsorption of the urate anion transporter-1 (URAT-1). Therefore, URAT-1 inhibition will promote uric acid excretion and reduce the risk of having gout. Dillenia philippinensis Rolfe, often known as katmon, is an endemic plant in the Philippines with bioactive compounds associated with several therapeutic benefits. The present study represents the first scientific inquiry into the antihyperuricemic potential of compounds isolated from D. philippinensis. This study aimed to assess the interaction of URAT-1 with the bioactive compounds present in katmon through molecular docking and evaluated the pharmacological properties of the compounds. Finally, alanine scanning and molecular dynamics simulation (MDS) were performed with the best-hit compound. The results in molecular docking revealed two compounds with the most stable interaction and high potency. Hence, they were deemed hit compounds. Moreover, pharmacological profiling of these compounds showed that only maslinic acid got accepted remarks based on the Lipinski rule. Additionally, the compound obtained notable results in the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) assessment. These profiles considered maslinic acid as the best-hit compound. The scanning depicted glutamine 149 as the most significant amino acid in the protein-ligand interaction. Further, relative stable dynamics were obtained in the URAT-1-maslinic acid complex compared to the free protein based on the Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) values. Our results established the potential antihyperuricemic property of maslinic acid from katmon via URAT-1 inhibition and may exhibit promising pharmacology.