Cytotoxic trans-platinum(II) complex with 3-hydroxymethylpyridine: Synthesis, X-ray structure and biological activity evaluation.

To assess the potential cytostatic properties of Pt(II) complexes with 3-hydroxymethylpyridine (3-hmpy) as the only carrier ligand, novel cis-[PtCl2(3-hmpy)2] (1) and trans-[PtCl2(3-hmpy)2] (2) have been prepared. Elemental analysis, FTIR spectroscopy, multinuclear NMR spectroscopy and X-ray crystallography were used to determine their structures. Based on the results obtained with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and clonogenic assay on T24 human bladder carcinoma cells (T24), the most potent compound 2 was further tested for cytotoxicity in human ovarian carcinoma cell lines - cisplatin sensitive (IGROV 1) and its resistant subclone (IGROV 1/RDDP). The cytotoxicity of compound 2 in IGROV 1/RDDP is comparable to cisplatin. Furthermore, compound 2 induced severe conformational changes in plasmid DNA, which resulted in a delayed onset of apoptosis in T24 cells, and higher amounts of Pt in tumours and serum compared to cisplatin. In addition, in vivo antitumour effectiveness was comparable to that of cisplatin with a smaller reduction of animals' body weight, thus demonstrating that it is a promising transplatin analogue which deserves further studies.

Structural and luminescent properties of Eu2+ and Nd3+-doped mixed alkaline earth aluminates prepared by the sol-gel method.

Alkaline earth aluminates with the overall nominal compositions Mg0.5Sr0.5Al2O4 (MSA), Ca0.5Mg0.5Al2O4 (CMA) and Ca0.5Sr0.5Al2O4 (CSA) doped with 0.5 mol% of Eu2+ and 0.25 mol% of Nd3+ ions were obtained by a modified aqueous sol-gel method and annealed in a reducing atmosphere at 900, 1000, 1100 and 1300 °C. The sample structures were investigated by XRD. Solid solubility was only confirmed for the CSA samples. UV-excited luminescence was observed in the blue region (λ = 440 nm) in the samples of CMA containing the monoclinic CaAl2O4 phase and in the green region (λ = 512 nm) in the samples of MSA containing hexagonal or monoclinic phases of SrAl2O4. The CSA samples, besides the blue region, exhibited an extended shoulder in the green region, which proved the existence of some pure strontium phases. Co-doped Nd3+ ions did not affect the wavelength of the emitted light, but the persistent luminescence at room temperature was greatly extended with respect to the aluminates doped with Eu2+ ions only.

Structural and Luminescent Properties of Eu2+-doped Aluminates Prepared by the Sol-gel Method.

Alkaline earth aluminates with the overall nominal compositions Mg0.5Sr0.5Al2O4 (MSA), Ca0.5Sr0.5Al2O4 (CSA) and Ca0.5Mg0.5Al2O4 (CMA) doped with 0.5 or 1 mol% of Eu2+ ions were obtained by a modified aqueous sol-gel method and annealed in a reductive atmosphere at 900, 1000, 1100 and 1300 °C. The sample compositions and their structures were studied by XRD employing the Rietveld method. Solid solubility was confirmed in CSA only, due to the similar ionic radii of Ca2+ and Sr2+. UV excited luminescence was observed in the blue region (λ = 440 nm) in samples of CSA and CMA containing the monoclinic phase of CaAl2O4 and in the green region (λ = 512 nm) in samples of MSA containing hexagonal or monoclinic phases of SrAl2O4.

Cytotoxicity of different platinum (II) analogues to human tumour cell lines in vitro and murine tumour in vivo alone or combined with electroporation.

BACKGROUND: The in vitro cytotoxic activity of two new platinum(II) complexes (3P-SK and PtAMP) in comparison with cisplatin (CDDP), oxaliplatin (OXA) and carboplatin (CARBO) was determined in four different human tumour cell lines. The in vivo efficiencies of CDDP and 3P-SK in MCA mammary carcinoma tumours induced in CBA mice were compared. MATERIALS AND METHODS: The in vitro cytotoxicity of the platinum (II) complexes was determined by the colorimetric MTT assay. The tumours were treated with different doses of platinum compounds, alone or combined with the local application of electric pulses to the tumour (electrochemotherapy). The antitumour effectiveness was determined by tumour growth inhibition. RESULTS: CDDP and OXA were the most cytotoxic in all cells tested. 3P-SK was more cytotoxic when compared to CARBO in all cells tested, except in MCF7. Intratumoral injection of 3P-SK alone or combined with electroporation (electrochemotherapy) induced significant tumour growth delay and tumour cure. CONCLUSION: 3P-SK was found to be less cytotoxic to human tumour cell lines than CDDP and OXA, but displayed a higher cytotoxicity compared to CARBO. In the experimental tumour model of mammary carcinoma, treatment with 3P-SK, alone or in combination with electroporation, was less effective compared to CDDP, but nevertheless resulted in tumour growth inhibition after a single application.

Crystal structures and cytotoxicity of isopropylamine Pt(II) complexes: a trinuclear squarato-bridged [Pt3(mu2-C4O4)3(H2NPri)6].3H2O and a mononuclear cis-[Pt(NO3)2(H2NPri)2].

Crystals of a novel platinum(II) complex with squarato ligand, [Pt(3)(mu(2)-C(4)O(4))(3)(H(2)NPr(i))(6)].3H(2)O (1) (H(2)NPr(i)=ipa), have been isolated from the aqueous solution of cis-[Pt(H(2)O)(2)(H(2)NPr(i))(2)]SO(4) and barium squarate. Slow evaporation of methanol solution of cis-[Pt(NO(3))(2)(H(2)NPr(i))(2)] (2) resulted in crystallization of nitrato complex. The single crystal X-ray diffraction method was used to determine structures of 1 and 2. Complex 1 crystallizes in a triclinic space group P1 with a=11.17380(10)A, b=14.4535(2)A, c=14.8010(2)A, alpha=86.0901(10) degrees , beta=78.4343(11) degrees , gamma=69.1915(5) degrees , and complex 2 in a monoclinic space group P2(1)/n, with a=10.1161(2)A, b=9.9188(2)A, c=13.3766(2)A, beta=102.7360(7) degrees . The X-ray structure analysis revealed that three platinum atoms in 1 are connected with three squarates which adopt bis(unidentate) binding modes. The squarato ligands span relatively long intramolecular Ptcdots, three dots, centeredPt distances (4.8842(3)-5.2699(3)A). A pair of cis positioned isopropylamine ligands completes a square planar coordination sphere of each Pt(II) ion. The square-planar coordination of complex 2 consists of two cis positioned isopropylamine ligands and two nitrato ligands. The results of cytotoxicity assay of trimer 1, monomer 2 and cis-diamminedichloroplatinum(II) (cisplatin) performed on human bladder tumor cell line T24 provide evidence that complex 2 is less cytotoxic compared to cisplatin and that the survival of tumor cells after exposure to 1 was minimally reduced.

Pt(II) complexes with N-(3-pyridyl)-2-(4-(trifluoromethyl)phenyl)diazenecarboxamide and their reactions with glutathione.

The reaction between [PtCl(dmso)(en)]Cl (dmso=dimethyl sulfoxide, en=ethylenediamine) and N-(3-pyridyl)-2-(4-(trifluoromethyl)phenyl)diazenecarboxamide (L) was studied using multinuclear NMR spectroscopy. The water-soluble complexes [PtCl(en)(L-N1)](+) (1) and [Pt(en)(L-N1)(2)](2+) (2) were isolated and their reactions with glutathione (GSH) were investigated to assess the oxidation properties of coordinated L. Both species 1 and 2 oxidized GSH to GSSG, while the reduced form of L (semicarbazide, SL) remained coordinated to Pt(2+). In complex 1 the labile chloride ion was substituted by the thiol moiety of GSH, which gave rise to the release of en in excess GSH over a period of 7 days. Complexes [PtCl(dmso)(en)]Cl, 1, 2 and ligand L were tested against T24 bladder carcinoma cells. Ligand L and complexes 1 and 2 showed higher cytotoxicity than [PtCl(dmso)(en)]Cl.