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Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand.

ABSTRACT: Two new ruthenium complexes, [Ru(?5-Cp)(PPh3)(2,2'-bipy-4,4'-R)]+ with R?=?-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 1.17?mg/L, presenting a LC50 of 5.73?mg/L at 5 days post fertilization.

SUBMITTER: Corte-Real L

PROVIDER: S-EPMC6345558 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand.

Côrte-Real Leonor L Karas Brittany B Gírio Patrícia P Moreno Alexis A Avecilla Fernando F Marques Fernanda F Buckley Brian T BT Cooper Keith R KR Doherty Cathleen C Falson Pierre P Garcia M Helena MH Valente Andreia A

European journal of medicinal chemistry 20181212

Two new ruthenium complexes, [Ru(η5-Cp)(PPh3)(2,2'-bipy-4,4'-R)]+ with R = -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 compou ...[more]

PMID: 30579125

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