Maltol-derived ruthenium-cymene complexes with tumor inhibiting properties: the impact of ligand-metal bond stability on anticancer activity in vitro.
Organometallic ruthenium-arene compounds bearing a maltol ligand have been shown to be nearly inactive in in vitro anticancer assays, presumably due to the formation of dimeric Ru(II) species in aqueous solutions. In an attempt to stabilize such complexes, [Ru(eta(6)-p-cymene)(XY)Cl] (XY=pyrones or thiopyrones) complexes with different substitution pattern of the (thio)pyrone ligands have been synthesized, their structures characterized spectroscopically, and their aquation behavior investigated as well as their tumor-inhibiting potency. The aquation behavior of pyrone systems with electron-donating substituents and of thiopyrone complexes was found to be significantly different from that of the maltol-type complex reported previously. However, the formation of the dimer can be excluded as the primary reason for the inactivity of the complex because some of the stable compounds are not active in cancer cell lines either. In contrast, studies of their reactivity towards amino acids demonstrate different reactivities of the pyrone and thiopyrone complexes, and the higher stability of the latter probably renders them active against human tumor cells.
Kandioller
Wolfgang
W
Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, Vienna, Austria.
Hartinger
Christian G
CG
Nazarov
Alexey A
AA
Bartel
Caroline
C
Skocic
Matthias
M
Jakupec
Michael A
MA
Arion
Vladimir B
VB
Keppler
Bernhard K
BK
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D011753:Pyrones; D017975:Ruthenium Compounds; C008316:maltol