Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025
A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents.
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Ortiz-Perez Eyra, Mendez-Alvarez Domingo, Juarez-Saldivar Alfredo, Moreno-Rodríguez Adriana, de Alba Alvarado Mariana, Gonzalez-Gonzalez Alonzo, Vazquez Karina, Martinez-Vazquez Ana Veronica, Nogueda-Torres Benjamin, Lara-Ramírez Edgar E, Paz-Gonzalez Alma D, Rivera Gildardo
Аннотация
BACKGROUND: 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.
OBJECTIVE: The aim in this study was identify potential α-TcCA inhibitors with trypanocidal activity.
METHODS: A maximum common substructure (MCS) and molecular docking were used to carried 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.
RESULTS: 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.
CONCLUSION: Compounds C7, C9, and C21 showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.
OBJECTIVE: The aim in this study was identify potential α-TcCA inhibitors with trypanocidal activity.
METHODS: A maximum common substructure (MCS) and molecular docking were used to carried 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.
RESULTS: 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.
CONCLUSION: Compounds C7, C9, and C21 showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.