VALORISASI AMPAS TEBU: STUDI MOLECULAR DOCKING SENYAWA FENOLIK SEBAGAI KANDIDAT INHIBITOR COX-2

Abstract

Cyclooxygenase-2 (COX-2) is an important target in anti-inflammatory therapy due to its role in the biosynthesis of pro-inflammatory prostaglandins. Phenolic compounds from natural sources, including those found in agroindustrial waste such as sugarcane bagasse, have been reported to possess potential as COX-2 inhibitors. This study aimed to evaluate the potential of phenolic compounds from sugarcane bagasse as candidate COX-2 inhibitors through molecular docking and ADMET prediction approaches. The analysis was conducted in silico using AutoDockTools 1.5.7, BIOVIA DSV, and pkCSM on 20 phenolic compounds. The COX-2 protein (6COX chain A) was prepared, and docking validation was performed via redocking of the reference ligand S58. Of the 20 compounds, 16 complied with Lipinski’s Rule of Five and exhibited favorable ADMET profiles, while 4 showed deviations. Docking validation yielded an RMSD of 1.17 Å, confirming the validity of the method. Four flavonoids (albainin A, australon A, luteolin, apigenin) demonstrated binding free energies ranging from −8.73 to −9.84 kcal/mol, comparable to the reference ligand S58 (−10.56 kcal/mol). Phytosterol even showed the lowest binding energy (−10.85 kcal/mol, Ki 11.15 nM), despite deviating from Lipinski’s criteria. Interaction analysis revealed the involvement of active residues Arg120, Tyr355, Ser353, Val523, and Phe518. These findings highlight that at least five phenolic compounds from sugarcane bagasse possess potential as natural COX-2 inhibitors, supporting the valorization of agroindustrial waste as a source of value-added bioactive compounds.