Iridium(III) Complexes of Terpyridine‐ and Terpyridine‐Analogous Ligands Bearing Sugar Residues and Their in vitro Activity

A series of terpyridine- and terpyridine-analogous ligands bearing sugar moieties (glucose, galactose) attached through different glycosidic bonds (S-glycosides, O-glycosides) and their iridium(III) complexes was synthesized and characterized. Their in vitro cytotoxicity was investigated, and one iridium complex with significant activity could be identified and studied in more detail. Dose-dependent inhibition of cell growth was achieved at low concentrations (5 µm). For reduction of proliferation by 50 % (ID50) the necessary concentration was 0.5 µm. The induction of apoptosis could be verified by flow-cytometric determination of DNA fragmentation in BJAB cells after 72 h. Apoptosis induction of the iridium complex in drug-resistant cells was tested with modified BJAB and Nalm-6 cells and their nonresistant strains. The complex was able to induce apoptosis in 50 % of cells (AC50) in concentrations of 30 µm in BJAB cells, 20 µm in Nalm-6 cells, 10 µm in resistant Nalm-6 cells, and 5 µm in resistant BJAB cells. Unspecific cell death was excluded by LDH-release assay.