Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand.
Eur J Med Chem
; 163: 853-863, 2019 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-30579125
ABSTRACT
Two new ruthenium complexes, [Ru(η5-Cp)(PPh3)(2,2'-bipy-4,4'-R)]+ with Râ¯=â¯-CH2OH (Ru1) or dibiotin ester (Ru2) were synthesized and fully characterized. Both compounds were tested against two types of breast cancer cells (MCF7 and MDA-MB-231), showing better cytotoxicity than cisplatin in the same experimental conditions. Since multidrug resistance (MDR) is one of the main problems in cancer chemotherapy, we have assessed the potential of these compounds to overcome resistance to treatments. Ru2 showed exceptional selectivity as P-gp inhibitor, while Ru1 is possibly a substrate. In vivo studies in zebrafish showed that Ru2 is well tolerated up to 1.17â¯mg/L, presenting a LC50 of 5.73â¯mg/L at 5 days post fertilization.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rutênio
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Biotina
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2,2'-Dipiridil
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Complexos de Coordenação
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article