{Reference Type}: Journal Article
{Title}: A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents.
{Author}: Ortiz-Pérez E;Mendez-Alvarez D;Juarez-Saldivar A;Rodriguez-Moreno A;De Alba-Alvarado M;Gonzalez-Gonzalez A;Vazquez K;Martinez-Vazquez AV;Nogueda-Torres B;Lara-Ramírez EE;Paz-Gonzalez AD;Rivera G;
{Journal}: Med Chem
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 30
{Factor}: 2.329
{DOI}: 10.2174/0115734064310458240719071823
{Abstract}: <B>BACKGROUND: </B>Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes.<BR><B>OBJECTIVE: </B>The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity.<BR><B>METHODS: </B>A maximum common substructure (MCS) and molecular docking were used to carry out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2.<BR><B>RESULTS: </B>Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi.<BR><B>CONCLUSIONS: </B>Compounds C7, C9, and C21 showed trypanocide activity; therefore, these results encourage the development of new trypanocidal agents based on their scaffold.