Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity.
Int J Parasitol Drugs Drug Resist
; 24: 100529, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38461700
ABSTRACT
Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC50 0.5 and 1.5 µM) but poorly selective (selectivity index <10). Here we extended the study to 33 new seleno-glycoconjugates with the aim to improve potency and selectivity. Three selenoglycosides and three glycosyl selenenylsulfides displayed IC50 against bloodstream Trypanosoma brucei in the sub-µM range (IC50 0.35-0.77 µM) and four of them showed an improved selectivity (selectivity index >38-folds vs. murine and human macrohages). For the glycosyl selenylsulfides, the anti-trypanosomal activity was not significantly influenced by the nature of the moiety attached to the sulfur atom. Except for a quinoline-, and to a minor extent a nitro-derivative, the most selective hits induced a rapid (within 60 min) and marked perturbation of the LMWT-redox homeostasis. The formation of selenenylsulfide glycoconjugates with free thiols has been identified as a potential mechanism involved in this process.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trypanocidal Agents
/
Trypanosoma
/
Trypanosoma brucei brucei
/
Trypanosomiasis, African
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Parasitol Drugs Drug Resist
Year:
2024
Document type:
Article
Affiliation country:
Uruguay