Influence of the anionic ligands on the anticancer activity of Ru(II)-dmso complexes: Kinetics of aquation and in vitro cytotoxicity of new dicarboxylate compounds in comparison with their chloride precursors.
We performed extensive studies on the kinetics of hydrolysis of a series of Ru(II)-dmso complexes containing dicarboxylate ligands, such as oxalate, malonate, succinate and 1,1-cyclobutane dicarboxylate (cbdc), derived from anticancer-active Ru(II)-dmso-Cl precursors. The in vitro antitumor activity of those compounds in comparison with their chloride precursors was evaluated against two tumor cell lines, the human KB oral carcinoma and the murine B16-F10 melanoma. The aim of this study was to assess how the nature of the anionic ligands (i.e. dicarboxylates vs. chlorides) affects the chemical behavior and the in vitro antitumor activity of Ru(II)-dmso complexes. Among the tested compounds only one complex, the dimer [fac-Ru(dmso-S)(3)(H(2)O)(mu-cbdc)](2) (5), exhibited moderate activity against both cell lines. Interestingly, this compound is the most kinetically stable in aqueous solution among those investigated. Despite the moderate in vitro activity, in an in vivo test, complex 5 exhibited no activity against both the primary tumor growth and the formation of spontaneous metastases on the MCa mammary carcinoma model.
Dipartimento di Scienze Chimiche, Università di Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy. jbratsos@units.it
Ioannis
I
Bratsos
Alberta
A
Bergamo
Gianni
G
Sava
Teresa
T
Gianferrara
Ennio
E
Zangrando
Enzo
E
Alessio
D000818:Animals; D000838:Anions; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007700:Kinetics; D008024:Ligands; D051379:Mice; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
D000838:Anions; D000970:Antineoplastic Agents; D002712:Chlorides; D008024:Ligands; D017975:Ruthenium Compounds; D014867:Water; D004121:Dimethyl Sulfoxide