Structure-activity relationships of novel N-imidazoylpiperazines with potent anti-Trypanosoma cruzi activity.
Future Med Chem
; 16(3): 253-269, 2024 02.
Article
in En
| MEDLINE
| ID: mdl-38193294
ABSTRACT
Background:
Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance.Methods:
Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed.Results:
Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives.Conclusion:
Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trypanocidal Agents
/
Trypanosoma cruzi
/
Chagas Disease
Limits:
Animals
Language:
En
Journal:
Future Med Chem
Year:
2024
Document type:
Article
Affiliation country: