Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs.
J Biol Inorg Chem
; 20(7): 1081-95, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26323351
ABSTRACT
The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence have been extensively studied in the laboratory setting, sometimes by generating fluorophore-tagged analogs. Here, we synthesized two Pt(II) complexes containing ethane-1,2-diamine ligands linked to a BODIPY fluorophore, and compared their biological activity with previously reported Pt(II) complexes conjugated to carboxyfluorescein and carboxyfluorescein diacetate. The cytotoxicity and DNA damage capacity of Pt-fluorophore complexes was compared to cisplatin, and the Pt-BODIPY complexes were found to be more cytotoxic with reduced cytotoxicity in cisplatin-resistant cells. Microscopy revealed a predominately cytosolic localization, with nuclear distribution at higher concentrations. Spheroids grown from parent and resistant cells revealed penetration of Pt-BODIPY into spheroids, and retention of the cisplatin-resistant spheroid phenotype. While most activity profiles were retained for the Pt-BODIPY complexes, accumulation in resistant cells was only slightly affected, suggesting that some aspects of Pt-fluorophore cellular pharmacology deviate from cisplatin.
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Base de dados:
MEDLINE
Assunto principal:
Platina
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Dano ao DNA
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Cisplatino
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Complexos de Coordenação
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Corantes Fluorescentes
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article