Thiazolidinones and related analogues as efficient antitrypanosomal agents
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
40885017
DOI
10.1016/j.bmc.2025.118363
PII: S0968-0896(25)00304-9
Knihovny.cz E-resources
- Keywords
- Animal African trypanosomiasis, Antiparasitic agents, Human sleeping sickness, Protozoan diseases, Thiazolidinediones, Trypanosoma brucei, Trypanosomiasis,
- MeSH
- Humans MeSH
- Molecular Structure MeSH
- Parasitic Sensitivity Tests MeSH
- Thiazolidinediones * pharmacology chemistry chemical synthesis MeSH
- Trypanocidal Agents * pharmacology chemistry chemical synthesis MeSH
- Trypanosoma brucei brucei drug effects MeSH
- Trypanosoma brucei rhodesiense * drug effects MeSH
- Trypanosomiasis, African drug therapy MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Thiazolidinediones * MeSH
- Trypanocidal Agents * MeSH
We designed and synthesised a series of thiazolidinediones and related analogues and evaluated their antiparasitic activity. A structure-activity relationship (SAR) study focused on modifications of specific parts of the molecule revealed derivatives that displayed significant activity against Trypanosoma brucei species. Notably, the analogue 6i exhibited exceptional activity, with an EC50 value of 30 nM and a selectivity index of >2000, against the protozoan Trypanosoma brucei rhodesiense, which causes human African trypanosomiasis. Additionally, compounds 6a, 6k, 7e, and 18 demonstrated antitrypanosomal activities in the less than 5 μM range. Our most active analogue 6i represents a promising candidate for further preclinical development.
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