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Dalton Trans. 2011 Jun 21;40(23):6216-25. doi: 10.1039/c0dt01452d. Epub 2011 Mar 3.

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

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1
Department of Chemistry, 1-014 Center for Science and Technology, College Place, Syracuse University, Syracuse, NY 13244, USA.

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 IC(50) 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.

PMID:
21369609
DOI:
10.1039/c0dt01452d
[Indexed for MEDLINE]

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