New palladium(II) and platinum(II) 5,5-diethylbarbiturate complexes with 2-phenylpyridine, 2,2’-bipyridine and 2,2’-dipyridylamine : synthesis, structures, DNA binding, molecular docking, cellular uptake, antioxidant activity and cytotoxicity

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Palladium(II) complexes of tridentate bis(benzazole) ligands: Structural, substitution kinetics, DNA interactions and cytotoxicity studies.

Reactions of 2,6-bis(benzimidazol-2-yl)pyridine (L1), 2,6-bis(benzoxazol-2-yl)pyridine (L2), and 2,6-bis(benzothiazol-2-yl)pyridine (L3) with [Pd(NCMe)2Cl2] in the presence of NaBF4 afforded the corresponding Pd(II) complexes, [Pd(L1)Cl]BF4, PdL1; [Pd(L2)Cl]BF4, PdL2; [Pd(L3)Cl]BF4, PdL3; respectively, while reaction of bis[(1H-benzimidazol-2-yl)methyl]amine (L4) with [Pd(NCMe)2Cl2] afforded complex [Pd(L4)Cl]Cl, PdL4. Characterisation of the complexes was accomplished using NMR, IR, MS, elemental analyses and single crystal X-ray crystallography. Ligand substitution kinetics of these complexes by biological nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5'-diphosphate disodium salt (5-GMP) were examined under pseudo-first order conditions. The reactivity of the complexes decreased in the order: PdL1 > PdL2 > PdL3 > PdL4, ascribed to electronic effects. Density functional theory (DFT) supported this trend. Studies of interaction of the Pd(II) complexes with calf thymus DNA (CT-DNA) revealed strong binding affinities via intercalative binding mode. Molecular docking studies established associative non-covalent interactions between the Pd complexes and DNA. The in vitro cytotoxic activities of PdL1-PdL4 were assessed in cancer cell lines HeLa and MRC5-SV2 and a normal cell line MRC-5, using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. PdL1 exhibited cytotoxic potency and selectivity against HeLa cell that was comparable to cisplatin's. Complex PdL1, unlike cisplatin, did not significantly induce caspase-dependent apoptosis

Di- and polynuclear silver(I) saccharinate complexes of tertiary diphosphane ligands: synthesis, structures, in vitro DNA binding, and antibacterial and anticancer properties

WOS: 000329236300003PubMed ID: 24132752A series of new silver(I) saccharinate (sac) complexes, [Ag-2(sac)(2)(mu-dppm)H2O]center dot H2O (1), {[Ag-2(mu-sac)(2)(mu-dppe)]center dot 3H(2)O center dot CH2Cl2} (n) (2), [Ag-2(mu-sac)(2)(mu-dppp)] (n) (3), and [Ag(sac)(mu-dppb)] (n) (4) [dppm is 1,1-bis(diphenylphosphino)methane, dppe is 1,2-bis(diphenylphosphino)ethane, dppp is 1,3-bis(diphenylphosphino)propane, and dppb is 1,4-bis(diphenylphosphino)butane], have been synthesized and characterized by C, H, N elemental analysis, IR spectroscopy, H-1 NMR, C-13 NMR, and P-31 NMR spectroscopy, electrospray ionization mass spectrometry, and thermogravimetry-differential thermal analysis. Single-crystal X-ray studies show that the diphosphanes act as bridging ligands to yield a dinuclear complex (1) and one-dimensional coordination polymers (2 and 4), whereas the sac ligand adopts a mu(2)-N/O bridging mode in 2, and is N-coordinated in 1 and 4. The interaction of the silver(I) complexes with fish sperm DNA was investigated using UV-vis spectroscopy, fluorescence spectroscopy, and agarose gel electrophoresis. The binding studies indicate that the silver(I) complexes can interact with fish sperm DNA through intercalation, and complexes 1 and 3 have the highest binding affinity. The gel electrophoresis assay further confirms the binding of the complexes with the pBR322 plasmid DNA. The minimum inhibitory concentrations of the complexes indicate that complex 1 exhibits very high antibacterial activity against standard bacterial strains of Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, being much higher than those of AgNO3, silver sulfadiazine, ciprofloxacin, and gentamicin. Moreover, complexes 1-3 exhibit very high cytotoxic activity against A549 and MCF-7 cancer cell lines, compared with AgNO3 and cisplatin. The bacterial and cell growth inhibitions of the silver(I) complexes are closely related to their DNA binding affinities.Uludag UniversityUludag University [UAP(F)-2011/36]Financial support received from Uludag University [project UAP(F)-2011/36] is gratefully acknowledged

Synthesis, crystal structures, in vitro DNA binding, antibacterial and cytotoxic activities of new di- and polynuclear silver(I) saccharinate complexes with tertiary monophosphanes

WOS: 000333790100004PubMed ID: 24480545Four new silver(I) saccharinate (sac) complexes, [Ag(mu-sac)(PPh3)](2) (1), [Ag(mu-sac)(PPh2CY)](2) (2), [Ag(mu-sac)(PPhCy2)](2) (3) and [Ag(mu-sac)(PCy3)](n) (4), where PPh3 = triphenylphosphane, PPh2Cy = cyclohexyldiphenylphosphane, PPhCy2 = dicyclohexylphenylphosphane and PCy3 = tricyclohexylphosphane, have been synthesized and fully characterized by elemental analysis, IR, NMR, ESI-MS and single crystal X-ray diffraction. Fluorescence ethidium bromide displacement indicate that all complexes bind to fish sperm (FS) DNA by intercalation with binding constants (K-A) of 29.1 +/- 0.26 x 10(5) M-1 for 1, 2.54 +/- 0.12 x 10(5) M-1 for 2, 2.42 +/- 0.08 x 10(5) M-1 for 3, 0.19 +/- 0.03 x 10(5) M-1 for 4. The relative viscosities of the FS-DNA solutions increase with increasing of the complex concentration, providing strong evidence for the intercalation mode. The gel electrophoresis assay further confirms their binding with the pBR322 plasmid DNA. The MIC values of the silver(I) complexes are generally higher than those of AgNO3 and silver sulfadiazine, but 1 presents a promising activity against Salmonella typhimurium and Staphylococcus aureus. All complexes are highly cytotoxic on human lung carcinoma (A549) and human breast adenocarcinoma (MCF-7) cell lines with IC50 values ranging from 0.82 to 3.13 mu M. (C) 2013 Elsevier B.V. All rights reserved.Uludag UniversityUludag University [UAP(F)-2011/36]We are grateful to Uludag University for the financial support given to the project (Project No: UAP(F)-2011/36)

Structures and biochemical evaluation of silver(I) 5,5-diethylbarbiturate complexes with bis(diphenylphosphino)alkanes as potential antimicrobial and anticancer agents

New silver(I) 5,5-diethylbarbiturate (barb) complexes with a series of bis(diphenylphosphino)alkanes such as 1,1-bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis-(diphenylphosphino)propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb) were synthesized and characterized. [Ag-2(barb)(2)(mu-dppm)(2) (1), [Ag-2(barb)(2)(mu-dppe)(DMSO)(2)] (2) and [Ag-2(barb)(2)( dppp)2](3) were binuclear, while [Ag(barb)(mu-dppb)] (4) was a coordination polymer. 1-4 effectively bind to the G/C rich region of the major groove of DNA and interact with BSA via hydrophobic interactions in accordance with molecular docking studies. All complexes displayed significant DNA cleavage in the presence of H2O2. 1-4 exhibited more specificity against Gram-positive bacteria than Gram-negative bacteria, but 2 targets both bacterial strains, being comparable to AgNO3 and silver sulfadiazine. Complex 1 has a strong growth inhibitory effect on A549 cells, while 2 and 3 exhibit considerable cytotoxicity against MCF-7 cells. The complexes showed high accumulation in the cytosol fraction of the cells. Mechanistic studies showed that 1 and 2 display effective cell growth inhibition by triggering S and G2/M phase arrest, induce apoptosis via mitochondrial pathways and also damage to DNA due to the overproduction of ROS. (C) 2017 Elsevier Masson SAS. All rights reserved

Ni( ii

New 5,5-diethylbarbiturate (barb) complexes of Ni(II), Cu(II) and Zn(II) with 1,10-phenanthroline (phen) and 2,2'-dipyridylamine (dpya), namely [Ni(phen-kappa N,N')(3)]Cl(barb)center dot 7H(2)O (1), [Cu(barb-kappa N)(barb-kappa N-2,O)(phen-kappa N,N')]center dot H2O (2), [Cu(barb-kappa N)(2)(phen-kappa N,N')] (2a), [Zn(barb-kappa N)(2)(phen-kappa N,N')]center dot H2O (3), [Ni(barb-kappa N-2,O) (dpya-kappa N,N')(2)]Cl center dot 2H(2)O (4), [Cu(barb-kappa N-2,O)(2)(dpya-kappa N,N')]center dot 2H(2)O (5) and [Zn(barb-kappa N)(2)(dpya-kappa N,N')] (6), were synthesized and characterized by elemental analysis, UV-vis, FT-IR and ESI-MS. The structures of the complexes were determined by X-ray crystallography. Notably, 3 and 6 were fluorescent in MeOH : H2O at rt. The interaction of the complexes with fish sperm (FS) DNA and bovine serum albumin (BSA) was investigated in detail by various techniques. The complexes exhibited groove binding along with a partial intercalative interaction with DNA, while the hydrogen bonding and hydrophobic interactions played a major role in binding to BSA. It is noteworthy that 2 exhibited the highest affinity towards DNA and BSA. Enzyme inhibition assay showed that 1-4 show a preference for both A/T and G/C rich sequences in pUC19 DNA, while 5 and 6 display a binding specificity to the G/C and A/T rich regions, respectively. These findings were further supported by molecular docking. The cellular uptake studies suggested that 2 was deposited mostly in the membrane fraction of the cells. Among the present complexes, 2 exhibited a very strong cytotoxic effect on A549, MCF-7, HT-29 and DU-145 cancer cells, being more potent than cisplatin. Moreover, 2 induces cell death through the apoptotic mode obtained by flow cytometry