Discovery of an orally active nitrothiophene-based antitrypanosomal agent.
Eur J Med Chem
; 263: 115954, 2024 Jan 05.
Article
in En
| MEDLINE
| ID: mdl-37984297
ABSTRACT
Human African Trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense and rhodesiense, is a parasitic disease endemic to sub-Saharan Africa. Untreated cases of HAT can be severely debilitating and fatal. Although the number of reported cases has decreased progressively over the last decade, the number of effective and easily administered medications is very limited. In this work, we report the antitrypanosomal activity of a series of potent compounds. A subset of molecules in the series are highly selective for trypanosomes and are metabolically stable. One of the compounds, (E)-N-(4-(methylamino)-4-oxobut-2-en-1-yl)-5-nitrothiophene-2-carboxamide (10), selectively inhibited the growth of T. b. brucei, T. b. gambiense and T. b. rhodesiense, have excellent oral bioavailability and was effective in treating acute infection of HAT in mouse models. Based on its excellent bioavailability, compound 10 and its analogs are candidates for lead optimization and pre-clinical investigations.
Key words
Full text:
1
Collection:
01-internacional
Health context:
3_ND
Database:
MEDLINE
Main subject:
Trypanocidal Agents
/
Trypanosoma brucei brucei
/
Trypanosomiasis, African
Limits:
Animals
/
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2024
Document type:
Article