ArticleMemorias do Instituto Oswaldo Cruz2025
Investigation of the activity of 4-aminoquinolines as cysteine protease inhibitors with application in the treatment of Chagas disease.
Article in Memorias do Instituto Oswaldo Cruz, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Pyridyl-Imidazopyridine Derivatives Displaying Submicromolar Activity Against Trypanosoma cruzi.ChemMedChem · 2026Article
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11 authors.
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Abstract
backgroundChagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi. The current drugs used to treat these diseases have limited efficacy and produce severe side effects. 4-aminoquinoline derivatives were shown to be a promising class of inhibitors of cysteine proteases cruzain and TbrCATL.
objectivesTo evaluate the trypanocidal activity of a new series of aminoquinolines as potential inhibitors of cruzain and TbrCATL.
methodsThree aminoquinolines were synthesised and their in vitro activity was evaluated against cruzain and TbrCATL as well as against amastigotes and trypomastigotes forms of T. cruzi. In silico studies were also carried out to try to understand the experimental results.
findingsCompound 5 showed promising activity against cruzain and TbrCATL, with better performance than E60, the reference drug. Compound 5 inhibited cruzain and TbrCATL at IC50 of 23 µM ±3 and 29 µM ±1, respectively, but this inhibition showed characteristics of promiscuous inhibition by colloidal aggregation. On the other hand, the compound 4 showed to be more promising activity against T. cruzi with IC50 2.57 µM ± 0.03 lower than the reference drug benznidazole 3.8 µM. MAIN
conclusionsThe results of this study can guide new drug development for the treatment of trypanosomiasis.
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