Computational docking toward cox-2 and synthesis of 4-formyl-2-methoxyphenyl-4-chlorobenzoate using microwave irradiation
DOI:
https://doi.org/10.46542/pe.2023.234.132136Keywords:
4-Formyl-2-methoxyphenyl-4-chlorobenzoate, Anti-inflammatory activity, Microwave irradiation, Molecular docking, SynthesisAbstract
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.
References
Agistia, D. D., Purnomo, H., Tegar, M., Nugroho, A. E. (2013). Interaction Between Active Compounds From Aegle marmelos Correa As Anti Inflammation Agent With Cox-1 And Cox-2 Receptor. Traditional Medicine Journal, 18(2), 80-87
Brayfield, A., (2014). Martindale The Complete Drug Reference 38th Edition. Pharmaceutical Press, London
Clayden, J., Greeves, N. and Warren, S. (2012). Organic Chemistry. Second Edition. Oxford University Press. https://doi.org/10.1007/978-3-642-34716-0
Ekowati, J., Diyah, N. W., Nofianti, K. A., Hamid, I. S., & Siswandono. (2018). Molecular docking of ferulic acid derivatives on P2Y12 receptor and their ADMET prediction. Journal of Mathematical and Fundamental Sciences, 50(2), 203–219. https://doi.org/10.5614/j.math.fund.sci.2018.50.2.8
Díaz-Ortiz, Prieto, P., & de la Hoz, A. (2019). A Critical Overview on the Effect of Microwave Irradiation in Organic Synthesis. Chemical Record, 19(1), 85–97. https://doi.org/10.1002/tcr.201800059
King, A. A., Shaughnessy, D. T., Mure, K., Leszczynska, J., Ward, W. O., Umbach, D. M., Xu, Z., Ducharme, D., Taylor, J. A., Demarini, D. M., & Klein, C. B. (2007). Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair. Mutation research, 616(1-2), 60–69. https://doi.org/10.1016/j.mrfmmm.2006.11.022
Lirdprapamongkol, K., Sakurai, H., Kawasaki, N., Choo, M. K., Saitoh, Y., Aozuka, Y., Singhirunnusorn, P., Ruchirawat, S., Svasti, J., & Saiki, I. (2005). Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 25(1), 57–65. https://doi.org/10.1016/j.ejps.2005.01.015
Maskeri, R., Ullal, S. D., Belagali, Y., Shoeb, A., Bhagwat, V., & Ramya. (2012). Evaluation of aphrodisiac effect of vanillin in male wistar rats. Pharmacognosy Journal, 4(32), 61–64. https://doi.org/10.5530/pj.2012.32.11
Mumtaza, I., Ekowati, J., & Nofianti, K. A. (2020). The effect of pyridine and triethylamine (tea) catalysts in the synthesis of the 4-benzoyloxy-3-methoxycinnamic acid through microwave irradiation method. European Journal of Molecular and Clinical Medicine, 7(1), 3884–3894
Nain, S., Singh, R., & Ravichandran, S. (2019). Importance of Microwave Heating In Organic Synthesis. Advanced Journal of Chemistry-Section A, 2(2), 94–104. https://doi.org/10.29088/SAMI/AJCA.2019.2.94104
Niazi, J., Kaur, N., Sachdeva, R., Bansal, Y., & Gupta, V. (2014). Antiinflammatory and antinociceptive activity of vanillin. Drug Development and Therapeutics, 5(2), 145. https://doi.org/10.4103/2394-2002.139630
Sharma, N., Sharma, U. K., & Van der Eycken, E. V. (2018). Microwave-Assisted Organic Synthesis: Overview of Recent Applications. Green Techniques for Organic Synthesis and Medicinal Chemistry, 441–468. https://doi.org/10.1002/9781119288152.ch17
Shivanika, C., Deepak Kumar, S., Ragunathan, V., Tiwari, P., Sumitha, A., & Brindha Devi, P. (2022). Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. Journal of Biomolecular Structure and Dynamics, 40(2), 585–611. https://doi.org/10.1080/07391102.2020.1815584
Siswandono. (2016). Kimia Medisinal Edisi Kedua. Surabaya: Airlangga University Press
Solomons, G., Fryhle, C., Snyder, S. 2016. Organic Chemistry 12nd Edition. USA: John Wiley & Sons, Inc
Tai, A., Sawano, T., Yazama, F., & Ito, H. (2011). Evaluation of antioxidant activity of vanillin by using multiple antioxidant assays. Biochimica et biophysica acta, 1810(2), 170–177. https://doi.org/10.1016/j.bbagen.2010.11.004
Vinod, T.K., Hart, D.J., Craine,L.E., Hart, H. (2012). Laboratory Manual for Organic Chemisry: A Short Course. 13th Edition. USA: Mary Finch
