Computational docking toward cox-2 and synthesis of 4-formyl-2-methoxyphenyl-4-chlorobenzoate using microwave irradiation

Background: Structural modification of organic compounds is needed to increase their bioactivity. Vanillin has been reported to have various therapeutic effects such as antioxidant, antimutagenic, anti-invasive and metastatic suppression potential as well as anti-inflammatory and antinociceptive activity. To increase the activity of organic compounds, their lipophilic properties must be enhanced by modifying their structure. Objective: The phenolic hydroxyl group of vanillin can be modified by adding an aromatic ring, carbonyl, and halogen to improve its bioactivity. The 4-formyl-2-methoxyphenyl-4-chlorobenzoate is a vanillin derivative that has been modified at its phenolic hydroxyl. Method: In this study, the synthesis of 4-formyl-2-methoxyphenyl-4-chlorobenzoate was carried out by microwave irradiation with various powers of 120, 200 and 400 watts. The characterisations of the synthesised compound were carried out using FTIR,¹H-NMR and¹³C-NMR spectrophotometry. The molecular docking study used Autodock software with the COX-2 receptor (PDB ID: 6COX) as the target receptor. Result: Microwave powers of 120, 200 and 400 watts were used to synthesise the target compound and produced yields of 89.09%, 72.78% and 34.49%, respectively. Molecular docking at the COX-2 receptors was studied to predict the anti-inflammatory activity of the 4-formyl-2-methoxyphenyl-4-chlorobenzoate. The docking results showed that the binding energy of 4-formyl-2-methoxyphenyl-4-chlorobenzoate was lower on chain A of the receptor (-8.18 kcal/mol) than the starting material, vanillin (-4.96 kcal/mol). It predicted that 4-formyl-2-methoxyphenyl-4-chlorobenzoate had better activity than vanillin. Conclusion: 4-formyl-2-methoxyphenyl-4-chlorobenzoate was successfully synthesised indicating that it is essential for this compound to be further developed as an anti-inflammatory agent.