TY - JOUR
T1 - Redox-active antineoplastic ruthenium complexes with indazole: Correlation of in vitro potency and reduction potential
AU - Jakupec, Michael
AU - Reisner, Erwin
AU - Eichinger, Anna
AU - Pongratz, Martina
AU - Arion, Vladimir
AU - Galanski, Mathea Sophia
AU - Hartinger, Christian
AU - Keppler, Bernhard
N1 - Zeitschrift: Journal of Medicinal Chemistry
DOI: 10.1021/jm0490742
Coden: JMCMA
Affiliations: Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, A-1090 Vienna, Austria
Adressen: Keppler, B.K.; Institute of Inorganic Chemistry; University of Vienna; Waehringer Strasse 42 A-1090 Vienna, Austria; email: [email protected]
Source-File: ChemieErgScopus.csv
Import aus Scopus: 2-s2.0-17544381239
Importdatum: 09.01.2007 14:08:11
12.02.2008: Datenanforderung 2112 (Import Sachbearbeiter)
09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)
PY - 2005
Y1 - 2005
N2 - Antineoplastic ruthenium(III) complexes are generally regarded as prodrugs, being activated by reduction. Within a homologous series of ruthenium(III) complexes, cytotoxic potency is therefore expected to increase with increasing ease of reduction. Complexes of the general formula [RuIIICl (6-n)(ind)n](3-n)- (n = 0-4; ind = indazole; counterions = Hind+ or Cl-) and the compound trans-[RuIICl2(ind)4] have been prepared and characterized electrochemically. Lever's parametrization method predicts that a higher indazole-to-chloride ratio results in a higher reduction potential, which is confirmed by cyclic voltammetry. In vitro antitumor potencies of these complexes in colon cancer cells (SW480) and ovarian cancer cells (CH1) vary by more than 2 orders of magnitude and increase in the following rank order: [RuIIICl6]3- <[RuIIICl 4(ind)2]- <[RuIIICl 5(ind)]2- � [RuIIICl3(ind) 3] <[RuIIICl2(ind)4]+ ˜ [RuIICl2(ind)4]. Thus, the observed differences in potency correlate with reduction potentials largely, though not perfectly, pointing to the influence of additional factors. Differences in the cellular uptake (probably resulting from different lipophilicity) contribute to this correlation but cannot solely account for it. Œ 2005 American Chemical Society.
AB - Antineoplastic ruthenium(III) complexes are generally regarded as prodrugs, being activated by reduction. Within a homologous series of ruthenium(III) complexes, cytotoxic potency is therefore expected to increase with increasing ease of reduction. Complexes of the general formula [RuIIICl (6-n)(ind)n](3-n)- (n = 0-4; ind = indazole; counterions = Hind+ or Cl-) and the compound trans-[RuIICl2(ind)4] have been prepared and characterized electrochemically. Lever's parametrization method predicts that a higher indazole-to-chloride ratio results in a higher reduction potential, which is confirmed by cyclic voltammetry. In vitro antitumor potencies of these complexes in colon cancer cells (SW480) and ovarian cancer cells (CH1) vary by more than 2 orders of magnitude and increase in the following rank order: [RuIIICl6]3- <[RuIIICl 4(ind)2]- <[RuIIICl 5(ind)]2- � [RuIIICl3(ind) 3] <[RuIIICl2(ind)4]+ ˜ [RuIICl2(ind)4]. Thus, the observed differences in potency correlate with reduction potentials largely, though not perfectly, pointing to the influence of additional factors. Differences in the cellular uptake (probably resulting from different lipophilicity) contribute to this correlation but cannot solely account for it. Œ 2005 American Chemical Society.
M3 - Article
SN - 0022-2623
VL - 48
SP - 2831
EP - 2837
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 8
ER -
