The synthesis of
ruthenium(II) and
osmium(II) arene complexes with the closely related indolo[3,2-c]
quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-
ethane-1,2-
diamine (L ( 1 )) and N'-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-
diamine (L ( 2 )) and indolo[3,2-d]
benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-
ethane-1,2-
diamine (L ( 3 )) and N'-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-
diamine (L ( 4 )) of the general formulas [(eta(6)-
p-cymene)M(II)(L ( 1 ))Cl]Cl, where M is Ru (4) and Os (6), [(eta(6)-
p-cymene)M(II)(L ( 2 ))Cl]Cl, where M is Ru (5) and Os (7), [(eta(6)-
p-cymene)M(II)(L ( 3 ))Cl]Cl, where M is Ru (8) and Os (10), and [(eta(6)-
p-cymene)M(II)(L ( 4 ))Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, spectroscopy (IR, UV-vis, and NMR), and X-ray crystallography (L ( 1 ).HCl, 4.H(2)O, 5, and 9.2.5H(2)O). Structure-activity relationships with regard to cytotoxicity and cell cycle effects in human
cancer cells as well as
cyclin-dependent kinase (cdk) inhibition and
DNA intercalation in cell-free settings have been established. The
metal-free indolo[3,2-c]
quinolines inhibit
cancer cell growth in vitro, with IC(50) values in the high nanomolar range, whereas those of the related indolo[3,2-d]
benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of cdk2/
cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L ( 1 ) and 7 are not paralleled by a substantially higher
kinase inhibition compared with indolobenzazepines L ( 4 ) and 11, arguing for additional targets and molecular effects, such as intercalation into
DNA.