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

Abstract

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.

Keywords: Anti-thrombotic; COX-1; Chemoinformatics; Good health and well being; Vanillin.

Figure 1.

Visualization of interactions of amino acid with aspirin, native ligand, 4-formyl-2-methoxyphenyl benzoate.

Figure 2.

Visualization of hydrophobic environment of aspirin, native ligand, and 4-formyl-2-methoxyphenyl benzoate in binding interactions with COX-1.