Highly cytotoxic substitutionally inert rhodium(III) tris(chelate) complexes

• Verfasst von: Hackenberg, Frauke [VerfasserIn]
• Verfasst von: Oehninger, Luciano [VerfasserIn]
• Verfasst von: Alborzinia, Hamed [VerfasserIn]
• Verfasst von: Can, Suzan [VerfasserIn]
• Verfasst von: Kitanovic, Igor [VerfasserIn]
• Verfasst von: Geldmacher, Yvonne [VerfasserIn]
• Verfasst von: Kokoschka, Malte [VerfasserIn]
• Verfasst von: Wölfl, Stefan [VerfasserIn]
• Verfasst von: Ott, Ingo [VerfasserIn]
• Verfasst von: Sheldrick, William S. [VerfasserIn]
• Titel: Highly cytotoxic substitutionally inert rhodium(III) tris(chelate) complexes
• Titelzusatz: DNA binding modes and biological impact on human cancer cells
• Verf.angabe: Frauke Hackenberg, Luciano Oehninger, Hamed Alborzinia, Suzan Can, Igor Kitanovic, Yvonne Geldmacher, Malte Kokoschka, Stefan Wölfl, Ingo Ott, William S. Sheldrick
• E-Jahr: 2011
• Jahr: 21 April 2011
• Umfang: 9 S.
• Fussnoten: Gesehen am 26.07.2022
• Titel Quelle: Enthalten in: Journal of inorganic biochemistry
• Ort Quelle: New York, NY [u.a.] : Elsevier, 1979
• Jahr Quelle: 2011
• Band/Heft Quelle: 105(2011), 7, Seite 991-999
• ISSN Quelle: 1873-3344
• DOI: doi:10.1016/j.jinorgbio.2011.04.006
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Anticancer agents
• Sach-SW: Apoptosis
• Sach-SW: Cell metabolism
• Sach-SW: DNA binding
• Sach-SW: Polypyridyl ligands
• Sach-SW: Rhodium
• K10plus-PPN: 1811704891

Abstract

The antiproliferative properties and cellular impact of novel substitutionally inert rhodium(III) complexes of the types [Rh{(CH3)2 NCS2}2(pp)]Cl 3-5 (pp=5,6-Me2phen, dpq, dppz) and OC-6-23-[Rh(2-S-py)2(pp)]Cl 6 and 7 (2-S-py=pyridine-2-thiolate; pp=dpq, dppz) have been investigated for the adherent human cancer cell lines MCF-7 and HT-29 and for non-adherent Jurkat cells. Whereas CD and viscosity measurements indicate that the polypyridyl ligands of 4 and 5 intercalate into CT DNA, this is not the case for the analogous pyridine-2-thiolate complexes 6 and 7. Complexes 3-7 all exhibit a high antiproliferative activity towards MCF-7 and HT-29 cells, with IC50 values in the range 0.055-0.285μM. As established by online monitoring with a cell-based sensor chip, the highly cytostatic complex 6 (IC50=0.059 and 0.078μM) invokes an immediate concentration-dependent reduction of MCF-7 cell respiration and a time-delayed decrease in cellular impedance, which can be ascribed to the induction of cell death. Annexin V/PI assays demonstrated that 6 also has a pronounced antiproliferative activity towards Jurkat cells and that it invokes extensive apoptosis and high concentrations of reactive oxygen species in these leukemia cells. The observation of a dose-dependent inhibition of the oxygen consumption of isolated mice mitochondria indicates the involvement of an intrinsic mitochondrial pathway in this process.