Activity of some platinum(II/IV) complexes with edda-type ligands against human adenocarcinoma HeLa cells

Kaluđerović, Goran N.; Đinović, Vesna M.; Juranić, Zorica D.; Stanojković, Tatjana; Sabo, Tibor J.

doi:10.1080/00958970500404708

Cited by 13 publications

(5 citation statements)

References 9 publications

(10 reference statements)

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“…It was found that Pt II and Pt IV complexes with edda-type ligands have similar cytotoxicity and are generally less efficient than cisplatin. [14] On the other hand, Pt IV complexes with esterified eddatype ligands display greater anticancer activity than corresponding Pt II complexes and cisplatin, [15] causing very rapid ne-…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

et al. 2010

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The present study describes the synthesis and anticancer activity of novel octahedral Pt(IV) complexes with cyclohexyl functionalized ethylenediamine-N,N'-diacetate-type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s-cis is the preferred geometry of these Pt(IV) complexes with tetradentate-coordinated (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell-cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt(IV) complexes against various cancer cell lines (IC(50) range: 1.9-8.7 microM) was higher than that of cisplatin (IC(50) range: 10.9-67.0 microM) and proceeded through completely different mechanisms. Cisplatin induced caspase-dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt(IV) complexes caused rapid, caspase-independent, oxidative stress-mediated non-apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.

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Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

et al. 2010

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“…3,4 The commercially available cancer treatment drug Oxaliplatin is a platinum complex with the vicinal diamine supporting ligand (1R,2R)-cyclohexane-1,2diamine, 3 and other platinum complexes with chelating diamine supporting ligands are currently being studied further. [5][6][7][8][9][10][11][12] The laboratory synthesis of (racemic) bisindolines has been shown through only a few known methods in the primary literature, all of which are intramolecular reactions (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Bisindolines from the reaction of 3,5-dimethoxyaniline with vicinal diones

2014

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Substituted bisindolines were synthesized from the reaction of 3,5-dimethoxyaniline and vicinal diones (2,3butanedione, benzil, and 4-methylbenzil). The reaction of 3,5-dimethoxyaniline with 2,3-butanedione under polar acidic conditions proceeded with an unanticipated double cyclization reaction forming 2,2 0dimethyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-1. The reaction of 3,5-dimethoxyaniline with benzil under similar conditions did not form a bisindoline, but instead formed cis-1,2-diphenyl-2-[(3,5dimethoxyphenyl)imino]ethanone, 2. When the solvent, acid, and reaction temperature were changed for the reaction of 3,5-dimethoxyaniline with benzil, 3,3-diphenyl-4,6-dimethoxyindolin-2-one, 3 (an isomer of 2), and 2,2 0 -diphenyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-4, were isolated as major and minor products, respectively. Similarly, the reaction of 3,5-dimethoxyaniline with 4-methylbenzil produced a 1 : 1 mixture of cis-1-(4-methylphenyl)-2-phenyl-2-[(3,5-dimethoxyphenyl)-imino]ethanone, 6a, and cis-1- (3,5-dimethoxyphenyl)imino]ethanone, 6b, under polar acidic conditions and 3-(4-methylphenyl)-3-phenyl-4,6-dimethoxyindolin-2-one, (+/À)-7 and 2-(4-methylphenyl)-2 0phenyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-8, under apolar acidic conditions at elevated temperature. We propose the mechanism of bisindoline and indolinone formation to include a Friedel-Crafts type electrophilic attack on the electron rich aryl ring at the ring closing C-C bond forming steps, and further propose a common carbocationic monocyclized intermediate.

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“…Thereafter, a great number of transition metal complexes with EDDA and related ligands have been isolated, and some of them have been also well-characterized using different methods, including X-ray , diffraction, spectroscopic (IR, Raman, NMR, ESR, UV–vis, and CD) techniques, electrochemistry, kinetic and thermodynamic information, , hydrolysis phenomena, as well as condensation reactions . Nowadays, they have given rise to a wide range of applications in chemistry, biology, , and medicine. , …”

Section: Introductionmentioning

confidence: 99%

“…10 Nowadays, they have given rise to a wide range of applications in chemistry, 2 biology, 11,12 and medicine. 13,14 Among these complexes, the octahedral cobalt(III) chelates 15,16 [Co(EDDA-type)(L)] ± containing one of the tetradentate dianion ligands, EDDA (ethylenediamine-N,N′diacetate), DMEDDA (N,N′-dimethylethylenediamine-N,N′diacetate), DEEDDA (N,N′-diethylethylenediamine-N,N′-diacetate), and a bidentate ancillary ligand L are of particular interest, because they have played a prominent role as model systems in the stereochemical study of transition metal complexes.…”

Section: ■ Introductionmentioning

confidence: 99%

Theoretical Analysis of the Influence of Chelate-Ring Size and Vicinal Effects on Electronic Circular Dichroism Spectra of Cobalt(III) EDDA-Type Complexes

Wang

Jia

et al. 2013

J. Phys. Chem. A

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To assess the contributions of configurational and vicinal effects as well as chelate-ring size to rotational strengths, the geometries of a series of cobalt(III) complexes [Co(EDDA-type)(L)](±) with the tetradentate EDDA-type ligands, EDDA (ethylenediamine-N,N'-diacetate), DMEDDA (N,N'-dimethylethylenediamine-N,N'-diacetate), DEEDDA (N,N'-diethylethylenediamine-N,N'-diacetate), and a bidentate ancillary ligand L (L = ethylenediamine, oxalate, carbonate, (S)-alanine, and malonate) in aqueous solution have been optimized at the DFT/B3LYP/6-311++G(2d,p) level of theory. Based on the optimized geometries, the excitation energies and oscillator and rotational strengths have been calculated using the time-dependent density functional theory (TDDFT) method with the same functional and basis set. The calculated circular dichroism (CD) curves are in excellent agreement with the observed ones except for some small red or blue shifts in peak wavelengths. For the influence of chelate-ring size of the bidentate ligands on the CD intensities, a qualitative analysis together with the quantitative TDDFT calculation reveal that it depends on the symmetry of the cobalt-EDDA backbone. For the s-cis-isomers, the influence is negligible due to the perturbation is symmetric. For the uns-cis-isomers, the perturbation is unsymmetric. Since a small ring size means a large perturbation, this leads to the integral CD intensities decreasing with increasing the chelate ring size. The vicinal effects of asymmetric nitrogens incorporate both the substitutent effects and conformational relaxation effects, with the former being dominant. By analyzing the contributions of chiral arrays to rotational strengths, we found that the part of contributions dominated by the S-type chiral nitrogens could be considered as a good measure for the vicinal effects of chiral nitrogens. In addition, we found that the twist form (δ/λ) of the backbone ethylenediamine ring (E-ring) of the coordinated EDDA-type ligands is a key factor to understand the properties of these chelates, because it not only dominates the relative stabilities of the s-cis-Λ(SS)-diastereoisomers with the result that λ > δ but also affects the major CD band by changing the order of the first two transitions. Moreover, the twist angle of E-ring is inversely related to the vicinal effect of chiral nitrogens. These findings may help us to understand the chelate ring size as well as vicinal effect related chiroptical phenomenon of the cobalt EDDA-type chelates.

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Activity of some platinum(II/IV) complexes with edda-type ligands against human adenocarcinoma HeLa cells

Cited by 13 publications

References 9 publications

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

Bisindolines from the reaction of 3,5-dimethoxyaniline with vicinal diones

Theoretical Analysis of the Influence of Chelate-Ring Size and Vicinal Effects on Electronic Circular Dichroism Spectra of Cobalt(III) EDDA-Type Complexes

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