Molecular docking of 5-o-benzoylpinostrobin derivatives from Boesenbergia pandurata roxb. as anti-inflammatory.

Abstract

The use of NSAIDs, also known as non-steroidal anti-inflammatory drugs, has numerous adverse effects and consequences. For this reason, it is necessary to develop rational drugs as safer anti-inflammatory drugs with fewer side effects. Temu Kunci rhizome contains Pinostrobin (5-hydroxy-7-methoxyflavanone), which is believed to have anti-inflammatory properties. This study aims to determine the strongest antiinflammatory activity at the cyclooxygenase-2 (COX-2) receptor through the 5-O-Benzoylpinostrobin derivative design. Methods: AutoDockTools on the COX-2 receptor (PDB code: 5IKR) were used in molecular docking in this study. The metrics employed were binding afinity (ΔG), inhibition constant (Ki), which serve as indicators of affinities, and amino acid residue similarity, which serves as a measure of the similarity of interactions. Predictive scores were confirmed by Molecular Docking Simulation. The top five 5-O-Benzoylpinostrobin derivatives show a high affinity for the COX-2 receptor compared to Pinostrobin as a marker compound of Boesenbergia pandurata Roxb and furthermore give the lowest inhibition constant (Ki) and the highest negative binding free energy (ΔG), 35.40, 45.21, 54.75, 64.43, 76.97 nM and -10.16, -10.02, -9.91, -9.81, -9.7 kcal/mol. Interestingly, the five 5-O-Benzoylpinostrobin derivatives also have higher affinity than the native ligand Mefenamic acid, which is known to be a non-selective COX-2 inhibitor. The highest predicted affinity was shown by 4-Nitro-5-O-benzoylpinostrobin for the COX-2 receptor (PDP ID: 5IKR), with a higher predicted affinity for Mefenamic acid. The five selected 5-O-Benzoylpinostrobin derivatives were potent modifications of pinostrobin as an antiinflammatory because they showed a higher affinity than Pinostrobin and Mefenamic acid. This study demonstrated that it is highly feasible to produce and test the novel 5-OBenzoylpinostrobin derivative in vivo, specifically 4-Nitro-5-Obenzoylpinostrobin.