Synthesis, structural, magnetic and thermal studies of copper(II) 5,5-diethylbarbiturate complexes with nicotinamide, 2,2′-bipyridine and triethanolamine

Three new copper(II) 5,5-diethylbarbiturate (barb) complexes of nicotinamide (nia), 2,2′-bipyridine (bpy) and triethanolamine (tea), trans-[Cu(barb)2(nia)2]⋅2H2O (1), cis-[Cu(barb)2(bpy)]⋅3H2O (2) and [Cu2(barb)2(tea)2]⋅2H2O (3), were synthesized and characterized by elemental analysis, spectroscopic (UV-Vis and FTIR) and magnetic moment measurements. Single crystal X-ray crystallographic measurements showed that 1 and 2 are mononuclear, while 3 is binuclear, in which two copper centers were bridged by deprotonated ethanol groups of two tea ligands. The barb ligand in these complexes is a bidentate N, O-donor. Thermal analysis (TG/DTA) studies in air indicated that the complexes first dehydrated and then the decomposition of nia, bpy or tea ligands occurred. The last exothermic stage was associated with degradation of the barb moiety to yield CuO as the end product

Zn(ii), Cd(ii) and Hg(ii) saccharinate complexes with 2,6-bis(2-benzimidazolyl)pyridine as promising anticancer agents in breast and lung cancer cell lines via ROS-induced apoptosis

New Zn(ii), Cd(ii) and Hg(ii) complexes of saccharinate (sac) and 2,6-bis(2-benzimidazolyl)pyridine (bzimpy), [Zn(bzimpy)(2)](sac)(2)center dot 2H(2)O (Zn), [Cd(sac)(2)(bzimpy)] (Cd) and [Hg(sac)(2)(bzimpy)] (Hg), were prepared and fully characterized by spectroscopic methods and X-ray crystallography.In vitroanticancer screening in A549 (lung), MCF-7 (breast) and HT29 (colon) cell lines showed thatZnwas highly cytotoxic against A549 and MCF-7 cells with IC(50)values of 1.74 +/- 0.06 and 3.15 +/- 0.10 mu M, respectively, andHgdemonstrated potent cytotoxic activity in MCF-7 cells (8.61 +/- 0.98 mu M), whileCdand bzimpy exhibited moderate growth inhibitory activities in all of the cell lines. In addition, they showed significantly lower toxicity towards normal human breast epithelial MCF10A cells. Moreover, the complexes exhibited significantly high nuclease activity towards plasmid DNA and their interactions with DNA were assessed by gel electrophoresis and DNA docking.ZnandHginduced G0/G1 cell arrest and apoptotic cell death detectedviatypical DNA condensation/fragmentation, annexin V staining and caspase 3/7 activity in A549 and MCF-7 cells. These complexes further caused depolarization of mitochondria and oxidative damage of genomic DNA following excessive production of reactive oxygen species (ROS)

Novel 5-fluorouracil complexes of Zn(II) with pyridine-based ligands as potential anticancer agents

A series of novel Zn(II) complexes of 5-fluorouracilate (5-FU), namely (Zn(5-FU)(2)(bpy)] (1), [Zn(5-FU)(2)(phen)] (2), [Zn(5-FU)(2)(dpya)]center dot H2O (3), [Zn(5-FU)(2)(bpyma)]center dot 2H(2)O (4) and [Zn(5-FU)(2)(terpy)]center dot H2O(5), were synthesized and structurally characterized by spectroscopic methods and X-ray crystallography. 5-FU was coordinated to Zn(II) via the deprotonated N3 site and also presented the N1 and N3 linkage isomerism in 4 and 5 due to its tautomerism. The antiproliferative activity of the complexes was studied against lung (A549), breast (MDA-MB-231), colon (HCT116) and prostate (DU145) cancer cell lines. Complexes 1, 4 and 5 except 2 and 3 showed potent growth inhibitory activity towards selected cancer cells. Remarkably, 4 was highly cytotoxic towards A549 and MDA-MB-231 cell lines, being more active than the clinical drugs cisplatin and 5-FU. In addition, 4 was not toxic to normal lung cells (BEAS-2B). The complex exhibited a significantly high affinity towards DNA as assessed by gel electrophoresis and DNA docking. The mechanistic studies of 4 in A549 cells indicated that the complex induced apoptotic cell death as evidenced via caspase 3/7 activity, Bcl2 inactivation, annexin V and DAPI/PI staining. 4 further elevated the levels of reactive oxygen species (ROS), depolarized mitochondria and enhanced the expression of gamma-H2AX, thus contributing to its remarkable anticancer activity

Trans-Pd/Pt(II) saccharinate complexes with a phosphine ligand: Synthesis, cytotoxicity and structure-activity relationship

New trans-[Pd(sac)(2)(PPhMe2)(DMSO)]center dot H2O (Pd) and trans-[Pt(sac)(2)(PPhMe2)(2)]center dot H2O (Pt) complexes (sac = saccharinate and PPhMe 2 = dimethylphenylphosphine) were synthesized and characterized by elemental analysis, IR, NMR, ESI-MS spectral analyses and X-ray diffraction. The complexes were evaluated for their in vitro cytotoxicity against breast (MCF-7), colon (HCT116) and lung (A549) human cancer cell lines. The ATP viability assay displayed that Pd was biologically inactive, but Pt showed significant anticancer potency on MCF-7 cancer cells, similar to cisplatin. The results suggested that Pt targeted DNA, whereas Pd displayed higher binding affinity towards human serum albumin (HSA). Mechanism of action studies of Pt suggested apoptotic cell death due to significant increase in intracellular ROS (reactive oxygen species) levels, mitochondrial damage and formation of DNA double-strand breaks. Finally, this work represents a new example of potent transplatin anticancer complexes

New manganese(II), iron(II), cobalt(II), nickel(II) and copper(II) saccharinate complexes of 2,6-bis(2-benzimidazolyl)pyridine as potential anticancer agents

New mononuclear complexes [Mn(NO3)(sac)(H2O)(bzimpy)]center dot 2DMF (Mn), [Fe(sac)(2)(H2O)(bzimpy)]center dot 2H(2)O (Fe), [Co(bzimpy)(2)](sac)(2)center dot 2H(2)O (Co), [Ni(bzimpy)(2)](sac)(2)center dot H2O center dot i-PrOH (Ni) and [Cu(sac)(2)(bzimpy)]center dot 3DMF (Cu) (sac = saccharinate and bzimpy = 2,6-bis(2-benzimidazolyl)pyridine) were synthesized and structurally characterized by elemental analysis, UV-Vis, IR, ESI-MS and X-ray diffraction. The anticancer activity of the metal complexes against A549 (lung), MCF-7 (breast), HT29 (colon) cancer cells and MCF10A (normal human breast epithelial) cells was tested and compared with those of cisplatin and bzimpy. The complexes displayed potent cytotoxic activity especially in MCF-7 and A549 cell lines, but they were practically inactive against the normal cells. Mechanistic studies with Mn and Cu complexes on A549 cells indicated that the complexes induced G0/G1 arrest. Both complexes increased intracellular ROS (reactive oxygen species) levels and successfully caused both mitochondrial dysfunction and doublestrand DNA breaks. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-3/7 activation and reduced Fas expression indicated that Mn and Cu induced ROS-dependent mitochondria-mediated intrinsic apoptosis in A549 cells. (C) 2020 Elsevier Masson SAS. All rights reserved

Water-soluble copper(ii) 5-fluorouracil complexes bearing polypyridyl co-ligands: synthesis, structures and anticancer activity

Five newly synthesized copper(ii) 5-fluorouracil (5-FU) complexes of polypyridyl co-ligands with good solubility in water, namely [CuCl(5-FU)(bpy)(DMSO)] (1), [Cu(5-FU)(phen)2](5-FU)·4H2O (2), [Cu(5-FU)(dpya)2](NO3)·2.5H2O (3), [Cu(5-FU)(NO3)(bpyma)]·H2O (4) and [CuCl(5-FU)(terpy)] (5) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, dpya = 2,2′-dipyridylamine, bpyma = bis(2-pyridylmethyl)amine and terpy = 2,2′;6′,2′′-terpyridine), were characterized by elemental analysis and a number of spectrometric methods. The structures of complexes 1-5 were determined by X-ray crystallography and the copper(ii) ions were five coordinate. Cytotoxic activity of the complexes in four human cancer cell lines, A549 (lung carcinoma), MDA-MB-231 (breast carcinoma), HCT116 (colon carcinoma) and DU145 (prostate carcinoma), and a normal cell line, BEAS-2B (human lung epithelial), was determined by SRB assay and compared with that of 5-FU and cisplatin. The complexation of 5-FU together with polypyridyl ligands resulted in a significant increase in the cytotoxicity of the complexes, with complex 2 exhibiting the highest anticancer potency against all the cell lines, with HCT116 being the most sensitive. The mode of action of cell death for 2 was investigated using morphological imaging and cytometric analyses, including the capacity for induction of apoptosis, generation of reactive oxygen species, mitochondrial dysfunction and DNA damage

Structures and anticancer activity of chlorido platinum(II) saccharinate complexes with mono- and dialkylphenylphosphines

cis-[PtCl(sac)(PPh2Me)(2)] (1), cis-[PtCl(sac)(PPhMe2)(2)] (2), trans-[PtCl(sac)(PPh2Et)(2)] (3) and trans- [PtCl(sac) (PPhEt2)(2)] (4) complexes (sac = saccharinate) were synthesized and characterized by elemental analysis and spectroscopic methods. The structures of 2-4 were determined by X-ray single-crystal diffraction. The interaction of the complexes with DNA was studied various biochemical, biophysical and molecular docking methods. Only the cis-configured complexes (1 and 2) showed nuclease activity and their binding affinity towards DNA was considerably higher than those of their trans-congeners (3 and 4). The chlorido ligand in the cis-configured complexes underwent aquation, making them more reactive towards DNA. Furthermore, 1 and 2 exhibited anticancer potency on breast (MCF-7) and colon (HCT116) cancer cells similar to cisplatin, whereas 3 and 4 were biologicallly inactive. Mechanistic studies on MCF-7 cells showed that higher nuclear uptake, cell cycle arrest at the S phase, dramatically increased DNA double-strand breaks, apoptosis induction, elevated levels of reactive oxygen species (ROS) and high mitochondrial membrane depolarization greatly contribute to the anticancer potency of 1 and 2

Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress-induced apoptosis

A series of the structurally related platinum(II) saccharinate (sac) complexes with alkylphenylphosphines, namely cis-[Pt(sac)(2)(PPh2Me)(2)]center dot DMSO (1), cis-[Pt(sac)(2)(PPhMe2)(2)] (2), cis-[Pt(sac)(2)(PPh2Et)(2)] (3), and cis-[Pt(sac)(2)(PPhEt2)(2)]center dot 2DMSO (4), were synthesized and fully characterized; their structures were determined by X-ray crystallography. All the complexes were investigated for their anticancer potentials on three human cancer cells including A549 (lung), MCF-7 (breast), and HCT116 (colon) in addition to a noncancerous human bronchial epithelial cells (BEAS-2B). Specifically, 1 and 3 showed significant cytotoxic effects against MCF-7 and HCT116 cell lines in comparison to cisplatin, and were considered as the most potent ones in the series. The cytotoxic complexes were found to cleave DNA efficiently. In addition, the binding interactions of the complexes with DNA were confirmed by enzyme inhibition and molecular docking studies. Complexes 1 and 3 were capable of inducing apoptosis and arrested the cell cycle at the DNA synthesis (S) phase in MCF-7 cells. Furthermore, 1 and 3 caused the excessive generation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and double-strand DNA breaks

Pd(II) and Pt(II) saccharinate complexes of bis(diphenylphosphino) propane/butane: Synthesis, structure, antiproliferative activity and mechanism of action

[M(sac)(2)(dppp)] (1 and 2), [M(dppp)(2)](sac)(2) (3 and 4) and [M(sac)(2)(dppb)] (5 and 6) complexes, where M = Pd-II (1, 3 and 5) and Pt-II (2, 4 and 6), sac = saccharinate, dppp = 1,3-bis(diphenylphosphino)propane and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by IR, NMR, ESI-MS and X-ray diffraction. The anticancer activity of the complexes against human lung (A549), breast (MCF-7), prostate (DU145) and colon (HCT116) cancer cell lines showed that the cationic complexes of dppp (3 and 4) and neutral Pt complex of dppb (6) were the most active agents of series. 3 and 4 exhibited antiproliferative activity, while 6 was highly cytotoxic compared to cisplatin. These complexes were therefore subjected to further investigations to ascertain the possible role of lipophilicity, cellular uptake and DNA/EISA binding in their biological activity. Flow cytometry analysis revealed that complex 6 induced apoptotic cell death in A549 and HCT116 cells and caused the cell cycle arrest at the S phase and overproduction of reactive oxygen species (ROS), giving rise to mitochondria) depolarization and DNA damage. (C) 2018 Elsevier Masson SAS. All rights reserved

Post-Bypass Extensive Ascites due to Splanchnic Bypass and the Effectiveness of Hyperalimentation Treatment

Reperfusion edema may develop in the early periods of chronic ischemic tissue reperfusion. Reperfusion edema may be represented after the splanchnic bypass with ascites, abdominal distension, and liver and kidney function impairment. In this article, we are reporting the hyperalimentation treatment and its results for the common ascites and hepatorenal syndrome, after a coeliac and superior mesenteric artery bypass. [Arch Clin Exp Surg 2013; 2(2.000): 124-128