Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity.
Int J Parasitol Drugs Drug Resist
; 24: 100529, 2024 Apr.
Article
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| 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.
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Base de datos:
MEDLINE
Asunto principal:
Tripanocidas
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Trypanosoma
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Trypanosoma brucei brucei
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Tripanosomiasis Africana
Idioma:
En
Revista:
Int J Parasitol Drugs Drug Resist
Año:
2024
Tipo del documento:
Article