Chemoinformatics approach to design and develop vanillin analogs as COX-1 inhibitor

Published: 16 March 2023
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  • Norhayati Norhayati Master Program in Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
  • Juni Ekowati Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Drug Development Research Group, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
  • Nuzul Wahyuning Diyah Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Drug Development Research Group, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
  • Bimo Ario Tejo Department of Chemistry, Faculty of Science, Universiti of Putra Malaysia, Serdang, Malaysia.
  • Samar Ahmed Department of Clinical Pharmacy, Faculty of Pharmacy, Fayoum University, Fayoum; Egy Herbal Factory, Kom Oshim, Fayoum, Egypt.

Background: Coronary Heart Disease (CHD), commonly known as the silent killer, impacted the severity of COVID-19 patients during the pandemic era. Thrombosis or blood clots create the buildup of plaque on the coronary artery walls of the heart, which leads to coronary heart disease. Cyclooxygenase 1 (COX-1) is involved in the production of prostacyclin by systemic arteries; hence, inhibiting the COX-1 enzyme can prevent platelet reactivity mediated by prostacyclin. To obtain good health and well-being, the research of discovery of new drugs for anti-thrombotic still continue.

Objective: This study aims to predict the potential of 17 compounds owned by the vanillin analog to COX-1 receptor using in silico.

Methods: This research employed a molecular docking analysis using Toshiba hardware and AutoDock Tools version 1.5.7, ChemDraw Professional 16.0, Discovery Studio, UCSF Chimera software, SWISSADME and pKCSM, a native ligand from COX- 1 (PDB ID: 1CQE) was validated.

Results: The validation result indicated that the RMSD was <2 Å. The 4-formyl-2-methoxyphenyl benzoate compound had the lowest binding energy in COX-1 inhibition with a value of -7.70 Å. All vanillin derivatives show good intestinal absorption, and the predicted toxicity indicated that they were non-hepatotoxic. All these compounds have the potential to be effective antithrombotic treatments when consumed orally.

Conclusion: In comparison to other vanillin derivative compounds, 4-formyl-2-methoxyphenyl benzoate has the lowest binding energy value; hence, this analog can continue to be synthesized and its potential as an antithrombotic agent might be confirmed by in vivo studies.

Liang C, Zhang W, Li S, Qin G. Coronary heart disease and COVID-19: A meta-analysis. Med Clin (Barc) 2021;156:547–54. DOI:

Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: Acute and long-term implications. Eur Heart J 2020;41:1798–800. DOI:

Ashorobi D, Ameer MA, Fernandez R. Thrombosis. Tampa: StatPearls Publishing 2022.

Lavie CJ, Howden CW, Scheiman J, Tursi J. Upper gastrointestinal toxicity associated with long-term aspirin therapy: consequences and prevention. Curr Probl Cardiol 2017;42:146–64. DOI:

Wang Y, Johnston C, Bath PM, et al. Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): Rationale and design of a multicentre randomised trial. Stroke Vasc Neurol 2021;6:280–5. DOI:

Chen Y, Garcia De Lomana M, Friedrich NO, Kirchmair J. Characterization of the Chemical Space of Known and Readily Obtainable Natural Products. J Chem Inf Model 2018;58:1518–32. DOI:

Lo YC, Rensi SE, Torng W, Altman RB. Machine learning in chemoinformatics and drug discovery. Drug Discovery Today 2018;23:1538-46. DOI:

Rodrigues T. Harnessing the potential of natural products in drug discovery from a cheminformatics vantage point. Organic and Biomolecular Chemistry. Royal Society Chem 2017;15:9275–82. DOI:

Lucotti S, Cerutti C, Soyer M, et al. Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/ thromboxane A2. J Clin Invest 2019;129:1845–62. DOI:

Kirkby NS, Zaiss AK, Urquhart P, et al. LC-MS/MS Confirms That COX-1 Drives Vascular Prostacyclin Whilst Gene Expression Pattern Reveals Non-Vascular Sites of COX-2 Expression. PLoS One 2013;8:1–9. DOI:

Woolery-Lloyd H, Kammer JN. Treatment of Hyperpigmentation. Vol. 30, Seminars in Cutaneous Medicine and Surgery 2011:171–5. DOI:

Ekowati J, Diyah NW, Nofianti KA, et al. Molecular docking of ferulic acid derivatives on P2Y12 receptor and their ADMET prediction. J Math Fundam Sci 2018;50:203–19. DOI:

Gallage NJ, Hansen EH, Kannangara R, et al. Vanillin formation from ferulic acid in Vanilla planifolia is catalysed by a single enzyme. Nat Commun 2014;5. DOI:

Lin WY, Teng CM, Tsai IL, Chen IS. Anti-platelet aggregation constituents from Gynura elliptica. Phytochemistry [Internet]. 2000;53:833–6. Available from: DOI:

Lin WY, Kuo YH, Chang YL, et al. Anti-platelet aggregation and chemical constituents from the rhizome of Gynura japonica. Planta Med 2003;69:757–64. DOI:

Susilowati R, Siswandono. Prinsip-prinsip Rancangan Obat. Siswandono Soekardjo. Surabaya: Airlangga University Press 1999;167–183

Kaddouri Y, Bouchal B, Abrigach F, et al. Synthesis, Molecular Docking, MEP and SAR Analysis, ADME-Tox Predictions, and Antimicrobial Evaluation of Novel Mono-and Tetra-Alkylated Pyrazole and Triazole Ligands. J Chem 2021;2021. DOI:

Wagner JR, Churas CP, Liu S, et al. Continuous Evaluation of Ligand Protein Predictions: A Weekly Community Challenge for Drug Docking. Structure [Internet] 2019;27:1326-1335.e4. DOI:

Sahayarayan JJ, Rajan KS, Vidhyavathi R, et al. In-silico protein-ligand docking studies against the estrogen protein of breast cancer using pharmacophore based virtual screening approaches. Saudi J Biol Sci [Internet] 2021;28:400–7. DOI:

Systemes D. Biovia Discovery Studio ® 2017 Comprehensive Modeling and Simulations. 2017;4.

Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem 2015;58:4066–72. DOI:

Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:1–13. DOI:

Picot D, Loll PJ, Garavito RM. The X-ray crystal structure of the membrane protein prostaglandin H 2 synthase-1. Nature 1994;367:243–9. DOI:

Xiao W, Wang D, Shen Z, et al. Multi-body interactions in molecular docking program devised with key water molecules in protein binding sites. Molecules 2018;23. DOI:

Ramírez D, Caballero J. Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data? Molecules 2018;23:1–17. DOI:

Rachmania R., Supandi, Cristina F. Analisis Penambatan Molekul Senyawa Flavonoid Buah Mahkota Dewa (Phaleria macrocarpa (Scheff.) Boerl.) pada Reseptor a-Glukosidase sebagai Antidiabetes. Pharmacy 2016;13:239–51.

Idrees S, Ashfaq UA. Discovery and design of cyclic peptides as dengue virus inhibitors through structure-based molecular docking. Asian Pac J Trop Med 2014;7:513–6. DOI:

Umamaheswari M, Madeswaran A, Asokkumar K. Virtual Screening Analysis and In-vitro Xanthine Oxidase Inhibitory Activity of Some Commercially Available Flavonoids. Iran J Pharm Res IJPR 2013;12:317–23.

Saravanan KM, Senthil R. PreFRP: Prediction and visualization of fluctuation residues in proteins. J Nat Sci Biol Med 2016;7:124–6. DOI:

Scheiner S, Kar T, Pattanayak J. Comparison of various types of hydrogen bonds involving aromatic amino acids. J Am Chem Soc 2002;124:13257–64. DOI:

Arwansyah, Laksmi A. TI. Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen pada Kanker Prostat. Curr Biochem J 2014;1:11–9. DOI:

Lipinski C., Lombardo F, Dominy B., Feeney P. Experimental and computational approaches to estimare solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3–26. DOI:

Lipinski C., Lombardo F, Dominy B., Feeney P. Drug Discovery Today. Technologie 2004;1:337–41. DOI:

Karonen M, Virtanen V. Partition coefficients (logP) of hydrolysable tannins. Molecules 2020;25:3691. DOI:

Weni M, et al. In Vitro Study and Molecular Bonding of Bioactive Compounds Extracts and Fractions of Red Betel Leaf (Piper crocatum) as α-Glucosidase Inhibitors. Bogor (ID) 2018.

O’Hagan S, Kell D. The Apparent Permeabilities of Caco-2 Cells to Marketed Drugs: Magnitude, and Independence from Both Biophysical Properties and Endogenite Similarities. Peer J3 2015;1405. DOI:

Chlebek J, Korábečný J, Doležal R, et al. In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier. Molecules 2019;24:1340. DOI:

Norhayati, N., Ekowati, J., Diyah, N. W., Tejo, B. A., & Ahmed, S. (2023). Chemoinformatics approach to design and develop vanillin analogs as COX-1 inhibitor. Journal of Public Health in Africa, 14(s1).


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