Salinomycin Derivatives Kill Breast Cancer Stem Cells by Lysosomal Iron Targeting.
Chemistry
; 26(33): 7416-7424, 2020 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-32083773
ABSTRACT
Salinomycin (1) exhibits a large spectrum of biological activities including the capacity to selectively eradicate cancer stem cells (CSC), making it and its derivatives promising candidates for the development of drug leads against CSC. It has been previously shown that salinomycin and its C20-propargylamine derivative (Ironomycin (2)) accumulate in lysosomes and sequester iron in this organelle. Herein, a library of salinomycin derivatives is reported, including products of C20-amination, C1-esterification, C9-oxidation, and C28-dehydration. The biological activity of these compounds is evaluated against transformed human mammary epithelial HMLER CD24low /CD44high cells, a well-established model of breast CSC, and HMLER CD24high /CD44low cells deprived of CSC properties. Unlike other structural alterations, derivative 4, which displays a cyclopropylamine at position C20, showed a strikingly low IC50 value of 23â
nm against HMLER CD24low /CD44high cells. This study provides highly selective molecules to target the CSC niche, a potential interesting advance for drug development to prevent cancer resistance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piranos
/
Células-Tronco Neoplásicas
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Neoplasias da Mama
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Receptores de Hialuronatos
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Ferro
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Lisossomos
Limite:
Female
/
Humans
Idioma:
En
Revista:
Chemistry
Ano de publicação:
2020
Tipo de documento:
Article