Discovery of a New Potent N‐(piperidin‐4‐yl)‐1H‐pyrrole‐2‐carboxamide Inhibitor of Adenylyl Cyclase of G. lamblia. Biological Evaluation and Molecular Modeling Studies

VEGA HISSI, ESTEBAN GABRIEL; DE COSTA GUARDAMAGNA, ANTONELLA BELEN; GARRO, ADRIANA D.; FALCON, CRISTIAN R.; ANDERLUH, MARKO; TOMA?I?, TIHOMIR; KIKELJ, DANIJEL; YANEFF, AGUSTÍN; DAVIO, CARLOS A.; ENRIZ, RICARDO D.; ZURITA, ADOLFO R.

CHEMMEDCHEM

WILEY-V C H VERLAG GMBH

Año: 2021

1860-7179

In this work, we report a derivative of N-(piperidin-4-yl)-1Hpyrrole-2-carboxamide as a new inhibitor for adenylyl cyclase ofGiardia lamblia which was obtained from a study usingstructural data of the nucleotidyl cyclase 1 (gNC1) of thisparasite. For such a study, we developed a model for thisspecific enzyme by using homology techniques, which is thefirst model reported for gNC1 of G. lamblia. Our studies showthat the new inhibitor has a competitive mechanism of actionagainst this enzyme. 2-Hydroxyestradiol was used as thereference compound for comparative studies. Results in thiswork are important from two points of view. on the one hand,an experimentally corroborated model for gNC1 of G. lambliaobtained by molecular modelling is presented; on the otherhand, the new inhibitor obtained is an undoubtedly excellentstarting structure for the development of new metabolicinhibitors for G. lamblia.