Synthesis of a Fluorescent Analogue of Paclitaxel That Selectively Binds Microtubules and Sensitively Detects Efflux by P-Glycoprotein.
Angew Chem Int Ed Engl
; 56(24): 6927-6931, 2017 06 06.
Article
em En
| MEDLINE
| ID: mdl-28485901
ABSTRACT
The anticancer drug paclitaxel (Taxol) exhibits paradoxical and poorly understood effects against slow-growing tumors. To investigate its biological activity, fluorophores such as Oregon Green have been linked to this drug. However, this modification increases its polarity by approximately 1000-fold and reduces the toxicity of Taxol towards cancer cell lines by over 200-fold. To construct more drug-like fluorescent probes suitable for imaging by confocal microscopy and analysis by flow cytometry, we synthesized derivatives of Taxol linked to the drug-like fluorophore Pacific Blue (PB). We found that PB-Gly-Taxol bound the target protein ß-tubulin with both high affinity inâ
vitro and high specificity in living cells, exhibited substantial cytotoxicity towards HeLa cells, and was a highly sensitive substrate of the multidrug resistance transporter P-glycoprotein (P-gp).
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Assunto principal:
Paclitaxel
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Corantes Fluorescentes
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Microtúbulos
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Antineoplásicos Fitogênicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article