Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes

Savić, Andrija; Filipović, Lana; Aranđelović, Sandra; Dojčinović, Biljana; Radulović, Siniša; Sabo, Tibor J.; Grgurić-Šipka, Sanja

doi:10.1016/j.ejmech.2014.05.060

Cited by 33 publications

(27 citation statements)

References 65 publications

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“…The complex trans -[PtI 2 (L 1 ) 2 ] exceeded activity of cisplatin against the HeLa cells approximately by the factor of 6 (L 1 = dimethylamine) [10]. The effectivity of [PtI 2 (L 2 )] in the EA.hy 926 cancer cells was ca 6-times higher than that of cisplatin ; L 2 = isobutyl ester of ( S , S )-1,3-propanediamine- N , N` -di-2-(cyclohexyl)propanoic acid; EA.hy 926 = derived by fusing human umbilical vein endothelial cells with A549 cells [11]. However, only the platinum(II) iodido complexes of the different types, such as mixed-ligand [13] or dinuclear [14] N- heterocyclic carbene complexes, showed in vitro anticancer activity comparable with 1 – 8 , but the mentioned substances were found to be toxic to the non-cancerous MRC-5 human fibroblasts (see below).…”

Section: Resultsmentioning

confidence: 99%

“…For example, cis -[PtI 2 (NH 3 ) 2 ] showed in vitro antitumour activity against various cancer cell lines including both cisplatin -sensitive (IC 50 = 13.4 μM) and cisplatin -resistant (IC 50 = 4.2 μM) HCT116 colon cancer cell lines (IC 50 = 7.6, and 22.0 μM, respectively, for cisplatin ) [6]. Apart from that, many other platinum(II) iodido complexes of various types (monofunctional [7–8], bifunctional [9–11], mixed-ligand [12–13] and multinuclear [14] complexes) showed considerable potency connected with different mechanism of action from those of the clinically used platinum-based drugs. For example, both isomers of [PtI 2 ( ip am) 2 ] ( ip am = isopropylamine) showed high potency against a panel of human breast, cervix, non-small cell lung and colon carcinomas [9–10].…”

Section: Introductionmentioning

confidence: 99%

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Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes

et al. 2016

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A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1–8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0–3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin. From the mechanistic point of view, evaluated ex vivo by Western blot analyses on the samples of isolated tumour tissues, the treatment of the animals with complex 8, contrary to cisplatin, decreased the levels of tumour suppressor p53 and increased significantly the amount of intracellular anti-apoptotic protein MCL-1L (37 kDa). Additionally, the active form of caspase 3 was significantly elevated in the sample of tumour tissues treated with complex 8, indicating that the activation of p53-independent cell-death pathway was initiated. The light and electron microscopy observations of the cancerous tissues revealed necrosis as a dominant mechanism of cell death, followed by scarce signs of apoptosis. The additional results (e.g. in vitro interaction experiments with selected biomolecules, cell cycle perturbations, gel electrophoretic studies on pUC19 plasmid DNA) supported the hypothesis that the complexes might be involved in the mechanism of action quite different from cisplatin.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes

et al. 2016

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“…As the biological activity of proteins and enzymes bind up their metal center, many metal complexes have been considered potential chemotherapeutic agents and wide-ranging studies on the transition metal complexes of the heterocyclic ligand have been carried out. In addition to various oxidation states of metal ions, metal complexes have different geometries that can alter the chemical reactivity and coordination number [4,5]. The importance of metals or metal-containing compounds for the treatment of cancer has been known since the 16th century [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Although cisplatin and carboplatin, which are well known and the most effective anticancer drugs, are used widely, their resistance as well as toxic effects on healthy tissue have led to a need to create more effective new metal complexes with less toxicity. Metal complexes provide a broad platform for drug design in the field of anticancer therapy [4]. A relationship between metals and cancer treatment has been widely accepted by researchers.…”

Section: Introductionmentioning

confidence: 99%

Gold(III) compounds-mediated inhibition of lung cancer cell proliferation

Bostancıoğlu

Kaya²,

Koparal³

et al. 2016

Anti-Cancer Drugs

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Research on chemotherapeutics for lung cancer is crucial for designing a new therapeutic strategy against malignant lung tumors. Although radiotherapy and chemotherapy, which are not selective for cancer cells and exert toxic effects on healthy cells, have a limited advantage, they are the primary treatment modalities for non-small lung cancer. In addition to cytotoxicity, resistance of chemotherapeutics results in failure of treatment. This is why it is of utmost importance to focus on the creation of new chemotherapeutics without toxicity for the successful treatment and improved survival of cancer patients. New gold(III) and Pt(II) compounds were synthesized with a heterocyclic ligand using 2-phenylimidazo[4,5-f][1,10]phenanthroline as a ligand and bis-1,4-di[([1,10] phenanthroline-5-il)amino]-2-buten as a bridge molecule. The characterization of the compounds was carried out using a variety of spectroscopic methods (H NMR, IR, MS, and elemental analysis). Their antiproliferative, antitumoral, and apoptotic activities were determined. IR spectra and NMR results confirmed the formation of dinuclear heterocyclic complexes for two metal complexes. Cytotoxicity studies on lung cancer cells (A549) and healthy cells (CHL) showed a marked increase in cytotoxicity with the use of gold(III) complexes, and especially [Au(L)B](PF6)2 showed higher cytotoxic and apoptotic features than cisplatin at lower concentrations in cancer cells. These findings have been supported by results from DAPI staining and colorimetric measurement of the caspase-3 enzyme in both cell lines. Compounds showed selective toxicity on the cancer cells. In the light of the high efficacy of our newly synthesized gold complexes, they might be good and promising anticancer agents compared with cisplatin.

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“…Platinum therapy associated inadequacies such as acquired resistance [3] and toxic side effects [4] emphasizes the need for new anticancer drugs with new mechanisms of action. Several research groups showed that platinum (II) complexes have significant anti-tumor activities against different types of cancers in vitro and in vivo [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Anti-growth effect of a novel trans-dichloridobis[2-(2-hydroxyethyl)pyridine]platinum (II) complex via induction of apoptosis on breast cancer cell lines

Oral

Cevatemre

Sarimahmut

et al. 2015

Bioorganic & Medicinal Chemistry

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Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes

Cited by 33 publications

References 65 publications

Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes

Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes

Gold(III) compounds-mediated inhibition of lung cancer cell proliferation

Anti-growth effect of a novel trans-dichloridobis[2-(2-hydroxyethyl)pyridine]platinum (II) complex via induction of apoptosis on breast cancer cell lines

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