期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 27, 期 63, 页码 15773-15785出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202102751
关键词
bioorganometallics; biphenyl; cancer gold; chelates
资金
- CNRS
- National FT-ICR network [FR 3624 CNRS]
- BBSRC Norwich Research Park Biosciences Doctoral Training Partnership [BB/M011216/1]
- Sorbonne Universite
A library of eleven cationic gold(III) complexes with novel structures were synthesized and tested for their antiproliferative activity on cancer cells, showing contrasting effects on viability and two complexes with high activity or selectivity. Reactivity studies with biological molecules revealed unique behavior compared to known gold complexes, indicating a new mode of action.
A library of eleven cationic gold(III) complexes of the general formula [(C C)Au(N N)](+) when C C is either biphenyl or 4,4'-ditertbutyldiphenyl and N N is a bipyridine, phenanthroline or dipyridylamine derivative have been synthesized and characterized. Contrasting effects on the viability of the triple negative breast cancer cells MDA-MB-231 was observed from a preliminary screening. The antiproliferative activity of the seven most active complexes were further assayed on a larger panel of human cancer cells as well as on non-cancerous cells for comparison. Two complexes stood out for being either highly active or highly selective. Eventually, reactivity studies with biologically meaningful amino acids, glutathione, higher order DNA structures and thioredoxin reductase (TrxR) revealed a markedly different behavior from that of the well-known coordinatively isomeric [(C N C)Au(NHC)](+) structure. This makes the [(C C)Au(N N)](+) complexes a new class of organogold compounds with an original mode of action.
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