In Silico Evaluation of Quercetin and CAPE as Potential Anti-Inflammatory Agents Targeting COX-2
DOI:
https://doi.org/10.26538/tjnpr/v9i10.4Keywords:
Propolis, Quercetin, Caffeic Acid Phenethyl Ester, Anti-inflammatory, Cyclooxygenase-2Abstract
Propolis, has emerged as a promising candidate in this regard due to its active compounds, such as quercetin and caffeic acid phenethyl ester (CAPE).7,8 These compounds exhibit anti-inflammatory, making propolis a potential alternative to conventional nonsteroidal anti-inflammatory drugs (NSAID). This study evaluates the anti-inflammatory potential of quercetin and CAPE, compounds from propolis, through in silico analysis focusing on cyclooxygenase-2 (COX-2) inhibition. Toxicity predictions, molecular docking, and molecular dynamics simulations were used to assess their safety and efficacy. The COX-2 structure (PDB ID: 4PH9) was retrieved from the Protein Data Bank, and ligands (quercetin, CAPE, ibuprofen, aspirin, and vanillin) were prepared for docking. Toxicity assessments were conducted using PROTOX II and pkCSM, including AMES, LD50, skin sensitization, and hepatotoxicity tests. Molecular docking was performed using Dock 6.8, and protein-ligand interactions were validated by RMSD. Molecular dynamics simulations were carried out with Amber22, including energy minimization, solvation, and stability evaluation via RMSD, RMSF, and MM-GBSA calculations. Toxicity predictions indicated that quercetin and CAPE are safe, with negative results in mutagenicity, skin sensitization, and hepatotoxicity tests, and LD50 values supporting their therapeutic potential. Molecular docking showed strong binding of quercetin (-51.4 kcal/mol) and CAPE (-53.3 kcal/mol) to COX-2, outperforming ibuprofen and aspirin. Molecular dynamics simulations revealed stable protein-ligand interactions, with low RMSD (0.3–0.4 Å) and RMSF values, indicating high stability. MM-GBSA calculations confirmed the strong binding of quercetin (-35.4 kcal/mol) and CAPE (-33.0 kcal/mol). Quercetin and CAPE exhibit strong COX-2 binding and stability, alongside favorable safety profiles, supporting their potential as anti-inflammatory agents for further clinical investigation.
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