Molecular Modelling Study of Heteroarylamide/Sulfonamide Compounds with Antitrypanosomal Activity

According to the World Health Organization (WHO), Chagas disease (CD), whose etiological agent is Trypanosoma cruzi (T. cruzi) parasite, affects about eight million people, mainly in Latin America. The cruzain enzyme highlighted among main biological targets, since it most abundant of cysteine protease class from T. and involved entire life cycle essential regulating interaction between parasite host. drugs available for treatment CD usually have strong side effects, nitro(triazole/imidazole)-based heteroarylamide/sulfonamide compounds (HA/S) emerge with high antitrypanosomal potential. In this study, quantitative structure-activity relationship (QSAR) were built using partial least squares (PLS) regression, results robust adequate predicting proposing five new derivatives according statistical parameters. docking suggest that best-scored HA/S showed hydrogen bonds residuals comprise catalytic region enzyme. molecular dynamics (MD) simulations, performed different methods, revealed stability compound obtained by QSAR model addition a better binding free energy value than literature.