Synthesis, characterization and DNA binding studies of platinum(II) complexes with benzimidazole derivative ligands.

The aim of this study was to synthesize and evaluate plasmid DNA interaction of new platinum(II) complexes with some 2-substituted benzimidazole derivatives as carrier ligands which may have potent anticancer activity and low toxicity. Twelve benzimidazole derivatives carrying indole, 2-/or 3-/or 4-methoxyphenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 3,4,5-trimethoxystyryl, 3,4,5-trimethoxybenzylthio or dimethylamino ethyl groups in their position 2 and twelve platinum(II) complexes with these carrier ligands were synthesized. The chemical structure of the platinum complexes have been characterized by their elemental analysis and FIR, 1H NMR and mass spectra and their 1H NMR and FIR spectra were interpreted by comparison with those of the ligands. The interaction of all the ligands and their complexes with plasmid DNA and their restriction endonuclease reactions by BamHI and HindIII enzymes were studied by agarose gel electrophoresis. It was determined that complex 1 [dichloro-di(2-(1H-indole-3-yl)benzimidazole)platinum(II)·2H2O] has stronger interaction than carboplatin and complex 10 [dichloro-di(2-(3,4,5-trimethoxystyryl)benzimidazole)platinum(II)·2H2O] has stronger interaction than both carboplatin and cisplatin with plasmid DNA.

Synthesis of platinum(II) complexes of 2-cycloalkyl-substituted benzimidazoles and their cytotoxic effects.

Five novel Pt(II) complexes with some 2-cycloalkyl-substituted benzimidazole carrier-ligands were synthesized and evaluated for their in vitro cytotoxic activities against HeLa and OVCAR-3 cell lines. A cell viability test revealed that [dichloro-bis(2-cycloheptylbenzimidazole) platinum(II)] is less cytotoxic than cisplatin, and its cytotoxic effect can be compared with that of carboplatin. Flow cytometric analysis revealed that this complex at 117 µM concentration causes apoptosis in approx. 72 % of the OVCAR-3 cell population. In addition, the complex was found to cause an increase in the SubG1 population of both OVCAR-3 and HeLa cells and to cause less apoptosis in HeLa cells than cisplatin.

Synthesis, in-vitro cytotoxic activity and DNA interactions of new dicarboxylatoplatinum(II) complexes with 2-hydroxymethylbenzimidazole as carrier ligands.

OBJECTIVES: The aim of this study was to investigate the in-vitro cytotoxic activity of new platinum(II) complexes on the human HeLa (ER-), MCF-7 (ER+) and MDA-MB 231 (ER-) cell lines. Furthermore, we investigated plasmid DNA interactions and inhibition of BamHI and HindIII restriction enzyme activity of the complex 1-4,7. METHODS: Platinum(II) complexes were synthesised from precursor complexes of [PtL2 Cl2 ] and [PtL2 I2 ]. Their cytotoxic activity was tested by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Their plasmid DNA interactions and restriction enzyme activities were also investigated using the agarose gel electrophoresis method. KEY FINDINGS: The growth inhibitory effect results showed that the cytotoxicity of complex 2 was found to be the most active complex among the synthesised complexes. CONCLUSIONS: The MTT results showed that complex 2 was found to be cytotoxic equal to cisplatin and higher than carboplatin against the MCF-7 and MDA-MB-231 cell lines. Furthermore, the estrogen or progesterone co-treatment slightly increased the cytotoxicity of complex 2, the cisplatin and carboplatin compared with the complex 2 tested alone in 50 µm concentration. According to plasmid DNA interaction and the restriction studies, complexes 1-4,7 modified the tertiary structure of pBR322 plasmid DNA, and complexes 2-4 prevented enzyme digestion at high concentrations.

Examination of ethical dilemmas experienced by adult intensive care unit nurses in physical restraint practices.

Nurses are more likely to face the dilemma of whether to resort to physical restraints or not and have a hard time making that decision. This is a descriptive study. A total of 55 nurses participated in the research. For data collection, a question form developed by researchers to determine perceptions of ethical dilemmas by nurses in the application of physical restraint was used. A descriptive analysis was made by calculating the mean, standard deviation, and maximum and minimum values. The nurses expressed (36.4%) having difficulty in deciding to use physical restraint. Nurses reported that they experience ethical dilemmas mainly in relation to the ethic principles of nonmaleficence, beneficence, and convenience. We have concluded that majority of nurses working in critical care units apply physical restraint to patients, although they are facing ethical dilemmas concerning harm and benefit principles during the application.

Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands.

In the present study, four Pt(II) complexes with 2-ethyl (1)/or benzyl (2)/or p-chlorobenzyl (3)/or 2-phenoxymethyl (4) benzimidazole carrier ligands were evaluated for their in vitro cytotoxic activities against the human HeLa cervix, oestrogen receptor-positive MCF-7 breast, and oestrogen receptor-negative MDA-MB 231 breast cancer cell lines. The plasmid DNA interactions and inhibition of the BamHI restriction enzyme activities of the complexes were also studied. Complex 3 was found to be more active than carboplatin for all examined cell lines and comparable with cisplatin, except for the HeLa cell line.

Synthesis, characterization, cytotoxicity, and DNA binding of some new platinum(II) and platinum(IV) complexes with benzimidazole ligands.

In this study, two Pt(II) and three Pt(IV) complexes with the structures of [PtL(2)Cl(2)] (1), [PtL(2)I(2)] (2), [PtL(2)Cl(2)(OH)(2)] (3), [PtL(2)Cl(2)(OCOCH(3))(2)] (4), and [PtL(2)Cl(4)] (5) (L = benzimidazole as carrier ligand) were synthesized and evaluated for their in vitro antiproliferative activities against the human MCF-7, HeLa, and HEp-2 cancer cell lines. The influence of compounds 1-5 on the tertiary structure of DNA was determined by their ability to modify the electrophoretic mobility of the form I and II bands of pBR322 plasmid DNA. The inhibition of BamH1 restriction enzyme activity of compounds 1-5 was also determined. In general, it was found that compounds 1-5 were less active than cisplatin and carboplatin against MCF-7 and HeLa cell lines (except for 1, which was found to be more active than carboplatin against the MCF-7 cell line). Compounds 1 and 3 were found to be significantly more active than cisplatin and carboplatin against the HEp-2 cell line.

Synthesis, cytotoxicity, and DNA interactions of new cisplatin analogues containing substituted benzimidazole ligands.

Six new platinum(II) complexes with 1-H or methyl-2-chloromethyl or acetoxymethyl or 2'-hydroxyethylbenzimidazole carrier ligands were synthesized and evaluated for their reactivity against model nucleophile I(-), cellular uptake, and in vitro antiproliferative activities against the human MCF-7 breast and HeLa cervix cancer cell lines. The effect of the compounds on pBR322 plasmid DNA was studied by gel electrophoretic mobility measurements. Flow cytometric analysis was also carried out to study the effect of representative compounds 1 and 2, bearing 2-chloromethyl or -acetoxymethylbenzimidazole carrier ligands, on the cell cycle distribution of MCF-7 and HeLa cells, respectively. In general, it was found that Pt(II) complexes were less cytotoxic than cisplatin and were comparable to carboplatin. The results of the plasmid DNA interaction and the restriction studies suggest that changing the chemical structure of the benzimidazole ligands may modulate DNA binding mode and the sequence selectivity. Compounds 1 and 2 had no significant effect on the cell cycle profile of the cells used. However, compound 2 induced a significant increase in the SubG1 cell population at a concentration of 20 microM.

Synthesis, cytotoxic activity on MCF-7 cell line and mutagenic activity of platinum(II) complexes with 2-substituted benzimidazole ligands.

Four Pt(II) complexes with 2-H/or-methyl/or-aminomethylbenzimidazole or 1,2-dimethylbenzimidazole ligands as "non-leaving groups" were synthesized and their antiproliferative properties were tested against the human MCF-7 breast cancer cell line. The mutagenic potentials of the complexes were tested in Salmonella typhimurium strains TA 98 and TA 100 in the absence of S9 rat liver fraction. In general, Pt(II) complexes tested which were found to be less active than cisplatin, exhibited moderate in vitro cytotoxic activity on MCF-7 cell line. Among the complexes tested, Pt(II) complex with 2-aminomethylbenzimidazole ligand was found to be highly mutagenic in S. typhimurium TA 98 and low mutagenic in S. typhimurium TA 100. Pt(II) complex with 1,2-dimethylbenzimidazole was mutagenic only in S. typhimurium TA 98. The other two complexes were found to be non-mutagen in both strains.