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2000
Volume 32, Issue 35
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Chagas disease (CD), a life-threatening disease caused by , remains a significant global public health concern. The limited efficacy of the available drugs (nifurtimox and benznidazole), their severe adverse events, and the unsatisfactory outcomes of clinical trials drive the search for new, effective, and safe drugs.

Objective

This study describes the synthesis, structural characterization, and antiparasitic activity of novel pyrazole-benzimidazole derivatives against mammalian developmental stages of .

Methods

Phenotypic screening was used to assess the effect of pyrazole-benzimidazole derivatives against . Three-dimensional cardiac spheroids were employed to evaluate the toxic effect and drug efficacy. Molecular docking and cysteine protease activity were also performed.

Results

Pyrazole-benzimidazole derivatives showed activity against both trypomastigotes and intracellular amastigotes. Compounds (IC = 6.6 µM) and (IC = 9.4 µM) demonstrated the most potent activity with a high selectivity index (SI > 45) against intracellular amastigotes. Both compounds exhibited high efficacy on 3D cardiac spheroids, effectively reducing the parasite load by over 80%. Molecular docking analysis revealed that both compounds target the catalytic domain of cruzain through pi-stacking and hydrogen bonding interactions and inhibit cysteine protease. These derivatives also showed an additive effect in combination with the reference drug (Bz).

Conclusion

Our findings emphasize the significance of pyrazole-benzimidazole hybrids in the search for new anti- agents.

© 2025 Bentham Science Publishers
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Insights into the Antiparasitic Activity of Pyrazole-benzimidazole against Trypanosoma cruzi
Curr. Med. Chem. 32, 7938 (2025); https://doi.org/10.2174/0109298673342932241016032905
/content/journals/cmc/10.2174/0109298673342932241016032905
/content/journals/cmc/10.2174/0109298673342932241016032905
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  • Article Type:     Research Article
Keyword(s): 3D cardiac microtissue; benzimidazole; chagas disease; parasite recrudescence; pyrazole; Trypanosoma cruzi

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