Journal Information
Vol. 42. Issue S2.
Pages 100-101 (November 2020)
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Vol. 42. Issue S2.
Pages 100-101 (November 2020)
DOI: 10.1016/j.htct.2020.10.170
Open Access
L.T.T. Tobias, S.C.G. Gomes, L.L. Borges, T.M. Alquimim, L.S.F. Sá, M.H.D.S. Pitta, L.C. Pina, L.R. Pedro, R.M.M.O. Filho, G.C. Pina
Pontifícia Universidade Católica de Goiás (PUC Goiás), Goiânia, GO, Brazil
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Goals: The aim of this work was evaluate using in silico methods the troxerutin potential to thrombin inhibition. Material e metods: Compounds obtained from medicinal plants with anticoagulant and 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. Finally, pharmacophoric analysis and molecular docking were performed. Results: Among the molecules analyzed for anticoagulant and cardioprotective activities, classified as without pharmacodynamics and with favorable pharmacokinetic profiles, troxerutin, a natural flavanoid derivative, found in the Brazilian cerrado was the most promising and had the highest scores on the servers employed. By predicting the biological activity of this molecule, the effects that corroborated the hypothesis that troxerutin has a anticoagulant activity, such as hemostatic effect, vasoprotection, free radical scavenging, antioxidant, antithrombotic, vasodilator, platelet adhesion inhibitor, therapy for peripheral vascular disease and other descriptions that support the applicability of this species was confirmed. The aglyconated part of troxerutin is absorbable and thus does not present any cardiotoxicity. Evaluation of troxerutin on Pro-Tox II, revealed its toxicity at level 5, with 6 being the lowest. The analysis further revealed inactive hepatotoxicity, cytotoxicity, mutagenicity, carcinogenotoxicity and other toxicities with a propensity of 61% to 97%. Troxerutin fitted with required features of the pharmacophore model of thrombin inhibitors, and a greater part of the molecules was aligned. The three features shared between troxerutin and the thrombin inhibitors with the lowest IC50 values indicate that troxerutin may present this inhibitor activity, which was corroborated by molecular docking analysis. Discussion: This study showed that thrombin can be considered a potential target to the natural chemical marker troxerutin, which could explain its anticoagulant effects. Furthermore, there is relevant evidence about the anticoagulant effects of the troxerutin, such as anti-thrombotic, anti-fibrinolytic and rheological activities. To explore the key ligand-enzyme intermolecular interactions between troxerutin and human thrombin, molecular docking simulations were performed using a crystal structure of thrombin. Then, molecular docking was carried out to illustrate the binding mode of the selected flavonoid and the target. The troxerutin could be docked in the catalytic site of human thrombin, indicating that this compound could serve as competitive inhibitor of thrombin, explaining its anticoagulant effects. Thus, this study proposed a potential mechanism that would explain the effects of these species and others that present troxerutin in its composition, besides future assays employing this chemical marker could be corroborated by the data raised in this work. Conclusion: The in silico approach demonstrated that troxerutin is a promising thrombin inhibitor. In vitro and in vivo trials using thrombin have shown that it can be a starting point for the development of new therapeutic options with thrombin inhibitors.

Hematology, Transfusion and Cell Therapy

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