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

Abstract

Background: Structure modification of organic compounds is needed to increase their bioactivity. Vanillin has been reported to has various therapeutic effects such as antioxidant, antimutagenic, anti-invasive and metastatic suppression potential, anti-inflammatory and also antinociceptive activity. To increase the activity of organic compounds, we have to enhance the lipophilic properties by modifications of the structure. Objective: The phenolic OH of vanillin can be modified by adding aromatic ring, carbonyl, and halogen to improve its bioactivity. The 4-formyl-2-methoxyphenyl-4-chlorobenzoate is a vanillin derivative that has been modified to its phenolic –OH. Method: In this study, the synthesis of 4-formyl-2-methoxyphenyl-4-chlorobenzoate was carried out by microwave irradiation with various power of 120, 200 and also 400 watt. The characterizations of the synthesized compound were carried out using FTIR, 1H-NMR and 13C-NMR spectrophotometry. The molecular docking study used Autodock software with at the COX-2 receptor (PDB ID: 6COX) as target receptor. Result: We used the microwave’s power of 120, 200 and also 400 watt to synthesis the target compound and produced 89.09%, 72.78% and 34.49% yield, consecutively. Molecular docking study at the COX-2 receptors was performed to predict the anti-inflammatory activity of 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 4-formyl-2-methoxyphenyl-4-chlorobenzoate has better activity than vanillin. Conclusion: The 4-formyl-2-methoxyphenyl-4-chlorobenzoate  was successfully synthesized and this finding proves that this compound essentials to be developed furthermore as an anti-inflammatory agent.