Ni(II)/Cu(II)/Zn(II) 5,5-diethylbarbiturate complexes with 1,10-phenanthroline and 2,2 '-dipyridylamine: synthesis, structures, DNA/BSA binding, nuclease activity, molecular docking, cellular uptake, cytotoxicity and the mode of cell death

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

Synthesis, structures, DNA/protein binding, molecular docking, anticancer activity and ROS generation of Ni(II), Cu(II) and Zn(II) 5,5-diethylbarbiturate complexes with bis(2-pyridylmethyl) amine and terpyridine

A series of structurally related Ni(II), Cu(II) and Zn(II) 5,5-diethylbarbiturate (barb) complexes with bis(2-pyridylmethyl) amine (1-3) and terpyridine (4-6) were synthesized and characterized using elemental analysis, UV-vis, IR, and ESI-MS. Single-crystal X-ray diffraction analysis showed that all complexes are mononuclear. Interactions of the complexes with DNA and protein were studied in detail using experimental and molecular docking techniques, indicating that all the complexes bind to DNA, exhibiting non-covalent binding specificity for G/C and A/T rich regions via a partial intercalative/groove binding mode, and effectively quench the intrinsic fluorescence of BSA through intermolecular interactions. The Cu(II) complexes (2 and 5) displayed a moderate antioxidant activity. In vitro cytotoxicity of 1-6 towards four cancer cell lines was evaluated and compared with that of cisplatin. 2 and 5 showed potent and selective cytotoxic activity against MCF-7 cells, suggesting that the DNA/BSA binding affinity of both complexes correlates with their growth inhibition effects. Furthermore, both complexes induced apoptosis on MCF-7 cells as revealed using flow cytometry analysis. The cytotoxicity and apoptosis induction exerted by 2 and 5 were associated with production of reactive oxygen species (ROS)

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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