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

Abstract

Two novel paullone derivatives, namely, 6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L1) and 9-bromo-6-(alpha-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 degrees 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 degrees 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.

Synthesis and structural peculiarities of gallium Complexes with novel paullone derivatives

“…The result of the X-ray diffraction study of 4 is shown in Figure 2 exocyclic double bond at the amidrazone moiety, which is in accord with 1 H and 13 C NMR data for 4. Unlike, related amidine 1, derived from 2-picolylamine, adopts a configuration with an endocyclic double bond within the azepine ring [5].…”

“…Since lactams could be converted into amidines and hydrazones providing a binding site for metals, the synthesis of ruthenium complexes with 9-bromo-6-(α-picolylamino)-7,12-dihydroindolo [3,2-d][1]benzazepine (1, Fig. 1) [5,6] and a gallium complex with two N-(9-bromo-7,12-dihydroindolo [3,2-d][1]benzazepin-6(5H)-ylidene-N'-(2-hydroxybenzylidene)azine ligands (3, see Scheme 1) has been performed [7].…”

New ruthenium(II) complexes with N-alkylphenothiazines: Synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity

“…Their properties can be altered by the choice of the ligand, which means that complexes potentially have multiple applications [13e16] and the ability to mimic iron binding to biomolecules [11,17]. Many biological properties have been attributed to ruthenium complexes including antioxidant activity [18] and cytotoxicity [19,20].…”

Release studies from smart hydrogels as carriers for piroxicam and copper(II)–oxicam complexes as anti-inflammatory and anti-cancer drugs. X-ray structures of new copper(II)–piroxicam and –isoxicam complex molecules

“…The search of new metal based pharmaceutical compounds has acquired new impetus during the last few years with the aim to find species that have high activity, low toxicity and with the goal to circumvent the drug resistance [1][2][3][4][5][6][7]. Cancers, inflammations, and diseases of the immune system are often related each other and attract much research efforts.…”

“…It has been reported by others that treatments with non-steroidal-anti-inflammatory drugs (NSAIDs) protect against lung cancers and breast cancer [8]. The interest on metal complexes with drugs as ligands has much increased because of the improved activities of the complexes when compared to the free ligands and because multi-therapies can stem from the same coordination molecule [6,7,9,10]. Different active functions can be combined in the same molecule through coordination chemistry.…”