Study Molecular Docking of Cinnamoyl-Amino Acids as Inhibitors Bacterial Resistance Antibiotics Acinetobacter baumannii and Methicillin-resistant Staphylococcus aureus (MRSA)

Several derivatives of cinnamic acid modified with amino acid groups were investigated by molecular docking simulation in this research. Tests were conducted on the inhibition of bacteria that have resistance to antibiotics Acinetobacter baumanni (PDB ID: 4Y0A) and Methicillin-resistant Staphylococcus aureus (MRSA) (PDB ID: 4CJN). Molecular docking using Auto Dock 4.2, Auto Dock Tools 1.5 programs, and Lipinski’s Rule of Five were applied to the test compounds. Twenty compound designs were created using Chemdraw 19.1, and docking results were visualized using Biova Discovery Studio. The results of docking molecules to A. baumannii showed that cinnamoyl glutamine and cinnamoyl threonine were shown to have the highest inhibitory activity (ΔG -8.68 kcal/mol and ΔG -8.41 kcal/mol), respectively, in comparison to the native ligand (ΔG -7.40 kcal/mol) and control imipenem (ΔG -4.82 kcal/mol). Then, the docking results against MRSA showed the highest inhibitory activity obtained on cinnamoyl lysine and cinnamoyl arginine with binding energy values (ΔG -7.52 kcal/mol) and (ΔG -7.17kcal/mol) compared to native ligands (ΔG -5.09 kcal/mol) and control amoxicillin (ΔG -7.13 kcal/mol). All compounds fully comply with Lipinski’s Rule of Five except cinnamoyl arginine. Through the in-silico model approach, bioactive compounds resulting from cinnamic acid modification with amino acids are predicted to have potential activity against bacterial resistance in MRSA and A. baumannii. This study suggests that cinnamic acid might still have a curative effect, but with a completely different pathway and mechanism compared to its derivatives as hybrids with amino acid groups.