Synthesis and DNA-binding properties of apoptosis-inducing cytotoxic half-sandwich rhodium(III) complexes with methyl-substituted polypyridyl ligands

Geldmacher, Yvonne; Rubbiani, Riccardo; Wefelmeier, Pascal; Prokop, Aram; Ott, Ingo; Sheldrick, William S.

doi:10.1016/j.jorganchem.2010.10.034

Cited by 46 publications

(39 citation statements)

References 47 publications

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“…Whereas RhCp* complexes formed with 2-picolinic acid (pic) [12] and 3-hydroxy(thio)pyrones derivatized by morpholine, piperidine or N-methylpyrazine moieties [13] exhibited only poor or no bioactivity. Promising in vitro antiproliferative activities have been reported for the RhCp* complexes of (N,N) polypyridyl (pp) ligands by Sheldrick et al [14][15][16][17] possessing IC 50 values in the low micromolar range. However, the RhCp* complexes of the simplest bidentate alkylamino and aromatic N-donor ligands, namely ethylenediamine (en) and 2,2'-bipyridine (bpy) did not show significant cytotoxicity (IC 50 >100 μM measured in MCF-7 and HT-29 cells) [17].…”

Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Enyedy

Mészáros

Dömötör

et al. 2015

Journal of Inorganic Biochemistry

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Complex formation equilibrium processes of the (N,N) donor containing 2,2'-bipyridine (bpy) and ethylenediamine (en) with (η 5 -pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous solution via pH-potentiometry, 1 H NMR spectroscopy, and UV-Vis spectrophotometry in the absence and presence of chloride ions. 2+ , and formation of ternary HSA-RhCp*-ligand adducts was proved. In the case of the deferiprone complex, the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the compound.

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Section: Compounds Namely Imidazolium Trans-[tetrachlorido(dmso)(imimentioning

confidence: 99%

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Enyedy

Mészáros

Dömötör

et al. 2015

Journal of Inorganic Biochemistry

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“…In contrast, {(g 5 -C 5 Me 5 )Rh(III)} 2? complexes [5][6][7][8][9] and their Ir(III) analogues [7][8][9][10][11] containing polypyridyl and other chelating aromatic ligands were subsequently found to exhibit IC 50 values in the low micromolar range. Promising cell-deathinducing properties have also been established for Rh(III) complexes containing the facial j 3 S and j 3 N coligands 1,4,7-trithiacyclononane ( [9]aneS 3 ) [12,13] and tris(pyrazolyl)-methane (tpm) [14], as well as for the meridional trichlorido complexes mer-[RhCl 3 (DMSO)(pp)] (DMSO is dimethyl sulfoxide, pp is polypyridyl) [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…Whereas flow-cytometric measurements of DNA fragmentation have previously indicated that both 1 and its 5,6-Me 2 phen analogue 2 (Scheme 2) induce specific apoptotic cell death in BJAB lymphoma cells [6], the pronounced cytotoxicity of [(g 5 -C 5 Me 5 )RhCl(1,2-naphthoquinone-1-oximate)] towards the HeLa and HL60 cell lines was attributed to necrosis [8]. To further elucidate the nature of their cell death mechanisms, we have now investigated the impact of complexes 1 and 2 on both adherent MCF-7 cells and nonadherent Jurkat leukemia cells, and compared this with the effects of similar trichloridorhodium(III) complexes.…”

Section: Introductionmentioning

confidence: 99%

Cellular impact and selectivity of half-sandwich organorhodium(III) anticancer complexes and their organoiridium(III) and trichloridorhodium(III) counterparts

et al. 2012

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Half-sandwich organorhodium(III) complexes and their trichloridorhodium(III) counterparts are potent anticancer agents that enhance the formation of reactive oxygen species and invoke a strong induction of apoptosis in leukemia cells. The antiproliferative activity towards human MCF-7 and HT-29 adenocarcinoma cells of novel nonintercalating complexes containing the 5-substituted phenanthroline ligands 5,6-dimethylphenanthroline, 5-chlorophenanthroline, and 5-nitrophenanthroline (phen*) increases dramatically in the order [(η(5)-C(5)Me(5))IrCl(phen*)](CF(3)SO(3)) < [(η(5)-C(5)Me(5))RhCl(phen*)](CF(3)SO(3)) < mer-[RhCl(3)(DMSO)(phen*)] (DMSO is dimethyl sulfoxide). Improved activity was also achieved by attaching a cell-penetrating peptide to the dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligand of an organorhodium(III) complex. Whereas 5-substitution led to significant improvements in the activity of the organoiridium(III) and trichloridorhodium(III) compounds in comparison with the parent phenanthroline complex, the IC(50) values of their organorhodium(III) counterparts remained effectively invariable. The high activities of the trichloridorhodium(III) complexes (IC(50) = 0.06-0.13 μM) were accompanied by pronounced selectivity towards human cancer cells in comparison with immortalized HEK-293 cells. In contrast, [(η(5)-C(5)Me(5))RhCl(5,6-Me(2)phen)](CF(3)SO(3)) (phen is phenanthroline) was markedly more active towards BJAB lymphoma cells than ex vivo healthy leukocytes and caused an immediate decrease in cellular adhesion possibly associated with interactions with membrane proteins. Its dppz analogue invoked an initial increase in glycolysis to compensate for reduced respiration before inducing a delayed onset of cell death. Strong antimitochondrial activity with respiration impairment and release of cytochrome c was established for both complexes.

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“…[16] In contrast, Sheldrick and co-workers have found that a number of other polypyridyl-containing trichloro iridium and rhodium complexes surprisingly did not significantly interact with DNA. [17] To explore this issue further, we investigated the ability of the complexes 10-35, identified from the second round of screening, to interact with DNA by using fluorescence resonance energy transfer (FRET) melting experiments ( Figure S5 shows representative spectra for 12). Our results showed that the complexes exhibited minimal binding to DNA (see Table S2), thus suggesting that the mechanism of action of these complexes is unlikely to involve DNA binding.…”

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confidence: 99%

Antagonizing STAT3 Dimerization with a Rhodium(III) Complex

Liu

Leung

et al. 2014

Angewandte Chemie

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Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity.

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Synthesis and DNA-binding properties of apoptosis-inducing cytotoxic half-sandwich rhodium(III) complexes with methyl-substituted polypyridyl ligands

Cited by 46 publications

References 47 publications

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2ʹ-bipyridine and ethylenediamine and their interaction with human serum albumin

Cellular impact and selectivity of half-sandwich organorhodium(III) anticancer complexes and their organoiridium(III) and trichloridorhodium(III) counterparts

Antagonizing STAT3 Dimerization with a Rhodium(III) Complex

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