Synthesis, cytotoxicity and cellular uptake studies of N3 functionalized Re(CO)3 thymidine complexes

Mark D. Bartholomä, Anthony R. Vortherms, Shawn Hillier, John Joyal, John Babich, Robert Patrick Doyle, Jon A Zubieta

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Nucleoside-derived drugs play an important role in the treatment of cancer. Here, we present the synthesis and characterization of an intriguing series of N3 conjugated Re(CO)3 thymidine complexes. The complexes were characterized by NMR spectroscopy and mass spectrometry and their cytotoxicity was assessed against A549 cells. A similar dependence on the spacer length and the toxicity has been found for N3 functionalized complexes as recently reported for their C5′ counterparts. A remarkable cytotoxic complex 22, carrying a dodecylene spacer at position N3 with a bis-quinoline metal chelate moiety, with an IC50 value of 3.4 ± 1.6 μM, has been identified. Addition of a 100-fold excess of thymidine did not statistically reduce the observed cytotoxicity of all complexes. Cellular uptake studies of complex 22 have been performed by fluorescent microscopy, showing that compound 22 was clearly internalized into A549 cells. Temperature dependent uptake studies, blocking experiments with thymidine, and endosomal co-localization suggest that uptake of 22 occurs via passive diffusion and endocytosis.

Original languageEnglish (US)
Pages (from-to)6216-6225
Number of pages10
JournalDalton Transactions
Volume40
Issue number23
DOIs
StatePublished - Jun 21 2011

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Carbon Monoxide
Cytotoxicity
Thymidine
Nucleosides
Nuclear magnetic resonance spectroscopy
Mass spectrometry
Toxicity
Microscopic examination
Metals
Pharmaceutical Preparations
Experiments
Temperature

ASJC Scopus subject areas

  • Inorganic Chemistry

Cite this

Synthesis, cytotoxicity and cellular uptake studies of N3 functionalized Re(CO)3 thymidine complexes. / Bartholomä, Mark D.; Vortherms, Anthony R.; Hillier, Shawn; Joyal, John; Babich, John; Doyle, Robert Patrick; Zubieta, Jon A.

In: Dalton Transactions, Vol. 40, No. 23, 21.06.2011, p. 6216-6225.

Research output: Contribution to journalArticle

Bartholomä, Mark D. ; Vortherms, Anthony R. ; Hillier, Shawn ; Joyal, John ; Babich, John ; Doyle, Robert Patrick ; Zubieta, Jon A. / Synthesis, cytotoxicity and cellular uptake studies of N3 functionalized Re(CO)3 thymidine complexes. In: Dalton Transactions. 2011 ; Vol. 40, No. 23. pp. 6216-6225.
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