Triagem virtual por QSAR de macrolídeos para identificação de inibidores de proteína Tiorredoxina Glutationa Redutase de Schistosoma mansoni

Abstract

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.