期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 24, 期 24, 页码 6334-6338出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201800596
关键词
bioinorganic; cancer; copper; nuclear magnetic resonance; zinc
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN312575]
- NSERC Vanier Canada Graduate Scholarship
- Canadian Institutes of Health Research (CIHR)
- UBC
Low aqueous solubility is a major barrier to the clinical application of otherwise promising drug candidates. We demonstrate that this issue can be resolved in medicinal molecules containing potential ligating groups, through the addition of labile transition-metal ions. Incubation of the chemotherapeutic CX5461 with Cu2+ or Zn2+ enables solubilization at neutral pH but does not affect intrinsic cytotoxicity. Spectroscopic and computational studies demonstrate that this arises from coordination to the pyrazine functionality of CX5461 and may involve bidentate coordination at physiological pH.
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