Drug-protein in vitro and in silico interaction analysis with hemoglobin as a study model
DOI:
https://doi.org/10.11606/issn.2176-7262.rmrp.2021.172174Keywords:
Hemoglobin, Drug-Protein, Interaction, Molecular DockingAbstract
Study model: It is an in vitro experimental study with a computational approach. Objective: Analyze the presence of interaction between hydrophobic drugs bezafibrate and hydrochlorothiazide and hemoglobin to predict bioavailability changes as well as in the protein function Metodology: The in vitro tests to evaluate the interaction between the bovine hemoglobin and bezafibrate and hydrochlorothiazide were perfomed by spectrophotometry; bioinformatic tools made interaction analysis and extrapolation for human hemoglobin. Results: The in vitro tests showed a decrease in the absorbance (k) at 405 nm equal to 8.75 x 10-4 min-1 for bezafibrate and 6.25 x 10-4 min-1 for hydrochlorothiazide. The decrease suggests an interaction between the drugs and hemoglobin, for bezafibrate this interaction seems to be stronger than hydrochlorothiazide. The in silico analysis showed that the drugs bind to the protein portion of the hemoglobin. The binding affinity constant obtained by molecular docking from bezafibrate and bovine hemoglobin (-8.3 Kcal/mol) sustain the experimental value of k and the greater number of interactions observed in relation to hydrochlorothiazide (-6.6 kcal/mol). The same pattern was observed for interaction of bezafibrate (-7.6 kcal/mol) and hydrochlorothiazide (-6.7 kcal/mol) with human hemoglobin. Conclusion: The spectrophotometry and bioinformatic methods suggested the possibility of hemoglobin interaction with hydrophobic drugs such as bezafibrate and hydrochlorothiazide; this interaction could affect the normal function of hemoglobin and change the pharmacodynamics and pharmacokinetics of drugs impairing their therapeutic efficiency.
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Copyright (c) 2021 Bianca Luiza Melo de Assis, Anderson Dillmann Groto, Gabrielle Caroline Peiter, Kádima Nayara Teixeira, Vitor Hugo Sales da Mota
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