Cardioprotective Effect of Troxerutin: An In silico Study

ABSTRACT

Background and Objective: Cardiovascular diseases are the leading causes of death worldwide. Therefore, the search for therapeutic alternatives is necessary, and in silico studies constitute an important tool for the development of cardioprotective drugs. The aim of this study was predicting the possible target which could explain the cardioprotective effects of the natural chemical marker troxerutin. Materials and Methods: Compounds with cardioprotective effects were selected using PubMed, ScienceDirect, and SciELO. The Molispiration server was used for oral bioavailability analysis, and Pred-HERG and Pro Tox-II were used to predict cardiac and systemic toxicities. Analyses of biological activities were performed in PASS online and those of molecular targets in Swiss Target Prediction and Superpred. Finally, pharmacophoric analysis and molecular docking were performed. To validate the model employed in molecular docking, redocking was also performed. Troxerutin, a natural flavonoid derivative, is found in the Brazilian Cerrado, extracted from Sophora japonica and Dimorphandra gardneriana. This molecule had the best scores and was thus selected for further analyses. To define the role of troxerutin as a thrombin antagonist, a pharmacophoric mapping was performed using five thrombin inhibitors with the lowest IC₅₀ values. Results: The results of PASS online corroborated with the cardioprotective effects of troxerutin, which were further confirmed by using thrombin, one of the targets obtained in the prediction studies. This interaction was verified by troxerutin docking with the human thrombin crystallographic structure (PDB ID: 2A2X). Redocking analysis established the parameters of the interaction model. As a result of thrombin antagonist, troxerutin interacted strongly with glycine and serine residues. Conclusion: Troxerutin is a promising thrombin inhibitor as demonstrated by pharmacophoric model and molecular docking analysis, which account for its use as a medical tool against cardiovascular disease.