Triagem virtual por QSAR de macrolídeos para identificação de inibidores de proteína Tiorredoxina Glutationa Redutase de Schistosoma mansoni
Resumo
Macrolides are obtained through their macrocyclic structure, containing a lactone forming
glycosidic linkages with sugars, as well as amide, amine, oxazole ring and thiazole groups.
Macrolides are a class of drugs widely used as antibacterials, with their most popular drugs
being Azithromycin, Erythromycin, and Clarithromycin. The presence is not such, the content
of the parasites and other surveys in the potential of repositioning the treatment of parasites and
between others. Most parasitic diseases are classified as neglected by the WHO. The diseases
neglected by schistosomiasis, infection by the parasite Schistosoma mansoni, which infect the
mother through contact with infected mollusks of the genus Biomphalaria, and stands out for
the high incidence in Brazil. With this, the computational indicators can help in the call of new
biological functions for this class, as well as the greater efficiency in no new treatment for
neglected diseases. Thus, a QSAR-based virtual screen by prediction of 3965 macrolides was
performed for biological research against Schistosoma mansoni, which may interact with the
molecular level of a protein Thioredoxin Glutathione Reductase (TGR) of S. mansoni. In the
development of macrolide molecules, of the predicted compounds in the QSAR-based virtual
screen, with the electron carrier site the SmTGR protein of the organism, to predict the probable
interactions that the drugs can perform with the macromolecule, in addition to the evaluation
of the predicted interactions. Through these analyses, it was possible to predict eight
compounds by QSAR with potential biological activity ≤ 10 μM, all with predictions of
biological activity ≥ 66%. Subsequently, the molecular binding of compounds with fewer IC50
was performed, resulting in the macrolide Sorangicin A, presenting the best interactions as well
as the best free energy (-8,141 Kcal/mol) with the primordial residues of the site (K124, R450,
R454, L581, H582, T584). Based on the results obtained in this study, it is noted that the drug
Sorangicin A, being used for alternative studies for the drug rifamycin possessing potential
treatment of people affected with schistosomiasis.