In vitro Assessment of Selected Benzoic Acid Derivatives as Anti-Inflammatory Compounds

Inflammation is a major reason of pathophysiology of several diseases, causing a number of disarrays. The present research involved exploring inhibition of soybean 5-lipoxygenase (5-LOX) by various benzoic acid derivatives (eudesmic acid, veratric acid, cumic acid, and syringic acid) and their kinetics studies, comparing with vanillin as a standard reference. Isothermal titration calorimetry (ITC) was performed to determine kinetics of the biomolecular interactions. Further, molecular docking studies were performed using GLIDE module of Schrodinger software to determine the inter-molecular interactions between the ligand and the target. Result underlined that four of the investigated derivatives exhibited potent inhibition of 5-LOX in a competitive manner with IC 50 values <60 μM. ITC study demonstrated that all derivatives bind effectively with a single domain of the target. Molecular docking studies revealed that all the four candidates displayed good interaction with the target. As found from Glide scores, veratric acid interacted stronger than other derivatives (GLIDE Score of -10.72 kcal/mol), forming two hydrogen bonds with residues GLN514 and GLN716, quite similar to the standard reference. ITC and GLIDE score analyses showed difference in the binding strength of the derivatives. This study would help in developing novel inhibitors, anti-inflammation as well as understanding mechanism(s) of ligand-enzyme interaction.