Trypanocidal and cell swelling activity of 20-deoxysalinomycin.
20-Deoxysalinomycin
African trypanosomiasis
Polyether ionophores
Trypanosoma brucei
Journal
Experimental parasitology
ISSN: 1090-2449
Titre abrégé: Exp Parasitol
Pays: United States
ID NLM: 0370713
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
05
09
2022
revised:
12
10
2022
accepted:
18
10
2022
pubmed:
24
10
2022
medline:
30
11
2022
entrez:
23
10
2022
Statut:
ppublish
Résumé
The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a four-fold higher selectivity compared to salinomycin. The stronger trypanocidal activity of 20-deoxysalinomycin is attributed to an enhanced ability to induce cell swelling in trypanosomes. The findings support 20-deoxysalinomycin as a useful lead in the rational development of new and improved anti-trypanosomal drugs.
Identifiants
pubmed: 36273616
pii: S0014-4894(22)00208-9
doi: 10.1016/j.exppara.2022.108414
pii:
doi:
Substances chimiques
Trypanocidal Agents
0
20-deoxysalinomycin
64003-50-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108414Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.