The First Ruthenium-Based Paullones: Syntheses, X-ray Diffraction Structures, and Spectroscopic and Antiproliferative Properties in Vitro

Two novel paullone derivatives, namely, 6-(α-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L1) and 9-bromo-6-(α-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L2), have been prepared. The reaction of cis-[RuCl2(DMSO)4] (DMSO = dimethyl sulfoxide)
with L1 and L2 in a 1:1 molar ratio
in dry ethanol at 50 °C afforded the complexes trans-[RuIICl2(DMSO)2L1] (1a) and trans-[RuIICl2(DMSO)2L2] (1b) in 26 and 30% yield,
respectively. The reaction carried out from the same starting compounds
in a 1:2 molar ratio at 75 °C led to the formation of [RuIICl(DMSO)(L1)2]Cl (2a) and [RuIICl(DMSO)(L2)2]Cl (2b) in 16 and 23% yield, correspondingly. The products were
characterized by elemental analysis, one- and two-dimensional NMR
spectroscopy, electrospray ionization mass spectrometry, IR spectroscopy,
electronic spectra, cyclic voltammetry, and X-ray crystallography
(L1, L2, 1a, and 2b). Complexes 2a and 2b exhibit
remarkable antiproliferative activity in three human carcinoma cell
lines, A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma),
and SW480 (colon carcinoma). The novel complexes show an intercalative
mode of interaction with DNA, which may render them attractive alternatives
to metal compounds with a coordinative mode of interaction.