Understanding the interactions of diruthenium anticancer agents with amino acids

The dinuclear anticancer agents 1,n-bis{chlorido[3-(oxo-kappa O)-2-methyl-4-(1H)-pyridinonato-kappa O4](eta(6)-p-cymene)-ruthenium(II)}alkane (PyRu2n) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein revealed uncommon protein-DNA and DNA-DNA crosslinking ability. We report here studies on the reactions of the diruthenium organometallics PyRu26 and PyRu28 in comparison with a mononuclear analogue PyRu3 with amino acids using mass spectrometry and NMR spectroscopy. The compounds behave very similarly, independent of the spacer length between the metal center and of the nuclearity of the complexes. Incubation with L-cysteine (Cys) results in fast release of the pyridone ligand, with the Ru complexes able to form Cys adducts. In contrast, L-methionine forms, initially, adducts with the metal centers, but over time, the adducts decompose. Similar behavior was observed for the reaction with L-histidine with [Ru(eta(6)-p-cymene)(L-histidine)] species detected.


Published in:
Journal Of Biological Inorganic Chemistry, 23, 7, 1159-1164
Year:
Oct 01 2018
Publisher:
New York, SPRINGER
ISSN:
0949-8257
1432-1327
Keywords:
Laboratories:




 Record created 2018-12-13, last modified 2019-06-19


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