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Updated: Sep 23, 2025

In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase
Published on: November 5, 2021
Novel trypanocidal thiophen-chalcone cruzain inhibitors: structure- and ligand-based studies
Aldo S de Oliveira1,2, Marilia Valli2, Leonardo Lg Ferreira2
1Federal University of Santa Catarina, Campus of Blumenau, Department of Exact Sciences & Education, Rua João Pessoa, 2750, Velha, Blumenau, SC, 89036-256, Brazil.
Abstract:
Background: Chagas disease is a neglected tropical disease that affects millions of people worldwide and for which no effective treatment is available. Materials & methods: 17 chalcones were synthesized, for which the inhibition of cruzain and trypanocidal activity were investigated. Results: Chalcone C8 showed the highest cruzain inhibitory (IC50 = 0.536 μm) and trypanocidal activity (IC50 = 0.990 μm). Molecular docking studies showed interactions involving Asp161 and the thiophen group interacting with the S2 subsite. Furthermore, quantitative structure-activity relationship (q2 = 0.786; r2 = 0.953) and density functional theory studies were carried out, and a correlation between the lowest unoccupied molecular orbital surface and trypanocidal activity was observed. Conclusion: These results demonstrate that these chalcones are worthwhile hits to be further optimized in Chagas disease drug discovery programs.
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