In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A

Trávníček, Zdeněk; Matiková-Maľarová, Miroslava; Novotná, Radka; Vančo, Ján; Štěpánková, Kamila; Suchý, Pavel

doi:10.1016/j.jinorgbio.2011.04.002

Cited by 36 publications

(8 citation statements)

References 61 publications

(65 reference statements)

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“…L-cysteine and reduced glutathione) were studied by means of mass spectrometry. Moreover, this work fits within the focus of our long term study dedicated to research and development of new transition metal complexes showing various types of biological effects, represented dominantly by the anticancer {Pt(II) [23], Pd(II) [24], Cu(II) [25], [26] or Ru(III) [27]}, anti-inflammatory {Au(I/III)} [15], [16], [28], antidiabetic and cytoprotective {Cu(II) [29]} activities.…”

Section: Introductionmentioning

confidence: 72%

Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

et al. 2014

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A series of gold(I) complexes involving triphenylphosphine (PPh3) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HLn) of the general composition [Au(Ln)(PPh3)] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC50 ≈ 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study.

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Section: Introductionmentioning

confidence: 72%

Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

et al. 2014

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“…The testing of in vivo antitumour activity was carried out according to the previously published procedure using the female DBA/2 SPF mice as experimental animals [26]. In this specific case, the animals were housed in the Sealsafe NEXT – IVC Blue Line Housing System (Tecniplast, Italy) to ensure the best possible experimental conditions and eliminate the risk of possible inter-group cross-contamination.…”

Section: Methodsmentioning

confidence: 99%

“…The tissue samples, obtained by the dissection of the sacrificed animals were divided into two parts, the first one was kept below −80°C for further evaluation by the methods of molecular biology, and the second one was processed by the histological procedures as described previously [26]. The paraffin embedded preparations were stained by the standard hematoxylin and eosin staining.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives

et al. 2014

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The in vitro antitumour activity studies on a panel of human cancer cell lines (A549, HeLa, G-361, A2780, and A2780R) and the combined in vivo and ex vivo antitumour testing on the L1210 lymphocytic leukaemia model were performed on the cis-[PtCl2(naza)2] complexes (1–3) involving the 7-azaindole derivatives (naza). The platinum(II) complexes showed significantly higher in vitro cytotoxic effects on cell-based models, as compared with cisplatin, and showed the ability to avoid the acquired resistance of the A2780R cell line to cisplatin. The in vivo testing of the complexes (applied at the same dose as cisplatin) revealed their positive effect on the reduction of cancerous tissues volume, even if it is lower than that of cisplatin, however, they also showed less serious adverse effects on the healthy tissues and the health status of the treated mice. The results of ex vivo assays revealed that the complexes 1–3 were able to modulate the levels of active forms of caspases 3 and 8, and the transcription factor p53, and thus activate the intrinsic (mitochondrial) pathway of apoptosis. The pharmacological observations were supported by both the histological and immunohistochemical evaluation of isolated cancerous tissues. The applicability of the prepared complexes and their fate in biological systems, characterized by the hydrolytic stability and the thermodynamic aspects of the interactions with cysteine, reduced glutathione, and human serum albumin were studied by the mass spectrometry and isothermal titration calorimetric experiments.

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“…Two ruthenium compounds, KP1019/NKP-1339 (indazolium or sodium salt of trans -[RuCl 4 (ind) 2 ]; ind = indazole) and NAMI-A ((imH)[ trans -RuCl 4 (DMSO)(im)]; im = imidazole), recently entered the clinical trials as prospective anticancer agents [ 8 , 9 ]. Many other ruthenium complexes were found to be highly in vitro and/or in vivo antitumor active against various types of tumors [ 10 , 11 ]. For example, complex [Ru( η 6 - p -cym)(L 1 )Cl](PF 6 ) was tested in vitro against ovarian A2780 (IC 50 = 16.2 μM), lung A549 (IC 50 = 10.5 μM), colon HCT116 (IC 50 = 3.4 μM) and breast (IC 50 = 12.1 μM) carcinoma human cancer cell lines; L 1 = N , N -dimethyl- N -[(2-pyridinyl)methylene]-1,4-benzenediamine [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Organometallic Half-Sandwich Dichloridoruthenium(II) Complexes with 7-Azaindoles: Synthesis, Characterization and Elucidation of Their Anticancer Inactivity against A2780 Cell Line

2015

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A series of organometallic half-sandwich dichloridoruthenium(II) complexes of the general formula [Ru(η 6-p-cym)(naza)Cl2] (1–8; p-cym = p-cymene; naza = 7-azaindole or its derivatives) was synthesised and fully characterized by elemental analysis, mass spectrometry, and infrared and multinuclear NMR spectroscopy. A single-crystal X-ray structural analysis of [Ru(η 6-p-cym)(2Me4Claza)Cl2] (6) revealed a typical piano-stool geometry with an N7-coordination mode of 2-methyl-4-chloro-7-azaindole (2Me4Claza). The complexes have been found to be inactive against human ovarian cancer cell line A2780 up to the highest applied concentration (IC50 > 50.0 μM). An inactivity of the complexes is caused by their instability in water-containing solvents connected with a release of the naza N-donor ligand, as proved by the detailed 1H NMR, mass spectrometry and fluorescence experiments.

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In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A

Cited by 36 publications

References 61 publications

Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

Pharmacological and Molecular Effects of Platinum(II) Complexes Involving 7-Azaindole Derivatives

Organometallic Half-Sandwich Dichloridoruthenium(II) Complexes with 7-Azaindoles: Synthesis, Characterization and Elucidation of Their Anticancer Inactivity against A2780 Cell Line

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