Computational investigation of Schiff bases from tryptamine as COX-2 inhibitors with potential anti-inflammatory activity

Abstract

Non-steroidal anti-inflammatory drugs are the most used drugs to inhibit cyclooxygenases (COX). Understanding the structure of COX isoforms is required for the research for more selective and less toxic anti-inflammatory agents. Also, computational methods can help to predict drug interaction. In this work, tryptamine Schiff bases, retrieved from literature, were screened to evaluate their ADMET profiles. After the initial screening, the compounds with better parameters were subjected to molecular docking interactions with the crystal structure of the COX-2 enzyme to verify binding affinities and the compound’s disposition as anti-inflammatory drugs. All compounds obeyed the Veber rule, and only one of them violated the Lipinski rule. Additionally, ten tryptamine Schiff bases presented equal or fewer toxicity alerts than Celecoxib (≤1). The binding affinities obtained through molecular docking for these Schiff bases varied from -9.974 to -8.765 kcal/mol. The results demonstrated that the chosen compounds showed higher binding affinities when compared to Celecoxib (-8.655 kcal/mol); this suggests a significant ability to inhibit the COX-2 enzyme. It has been proposed that the presence of phenolic hydroxyl is significant for the observed binding affinities. The results of this study indicate that tryptamine Schiff bases are promising candidates to treat inflammatory disorders, with the potential to be used as suitable medicines for pain and inflammation treatment.