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Volume 21, Issue 1
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Background

Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of (α-CA) 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-CA 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 model against the NINOA strain of and cytotoxicity was determined in a murine model of macrophage cells J774.2.

Results

Five sulfonamide derivatives (, , , , and ) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-CA and good biopharmaceutical and pharmacokinetic properties. , , and had half-maximal inhibitory concentration (IC) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of .

Conclusion

Compounds , and showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.

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A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents
Med. Chem. 21, 46 (2025); https://doi.org/10.2174/0115734064310458240719071823
/content/journals/mc/10.2174/0115734064310458240719071823
/content/journals/mc/10.2174/0115734064310458240719071823
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  • Article Type:     Research Article
Keyword(s): carbonic anhydrase; chagas disease; molecular docking; sulfonamides; Trypanosoma cruzi; virtual screening

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