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

Apoptosis-inducing effect of a palladium(II) saccharinate complex of terpyridine on human breast cancer cells in vitro and in vivo

The anti-growth effect of a palladium(II) complex-[PdCl(terpy)](sac)center dot 2H(2)O] (sac = saccharinate, and terpy = 2,2':6',2 ''-terpyridine)-was tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. Anti-growth effect was assayed by the MTT and ATP viability assays in vitro and then confirmed on Balb/c mice in vivo. The mode of cell death was determined by both histological and biochemical methods. The Pd(II) complex had anti-growth effect on a dose dependent manner in vitro and in vivo. The cells died by apoptosis as evidenced by the pyknotic nucleus, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the palladium(II) saccharinate complex of terpyridine represents a potentially active novel complex for the breast cancer treatment, thus warrants further studies. (C) 2014 Elsevier Ltd. All rights reserved

A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer

Several natural products have been suggested as effective agents for the treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in cancer, which is a trendy hypothesis, it is worth investigating the effects of pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB-231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and MCF-7s (cancer stem cell enriched population) cells was investigated by real time viability monitorization (xCELLigence System (R)) and ATP assay, respectively. Mode of cell death was evaluated using electron and fluorescence microscopies, western blotting (autophagy, apoptosis and ER-stress related markers) and flow cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions). Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells with IC50 values ranging at 0.38-1.75 mu M. It inhibited sphere formation at relatively lower doses (<1.56 mu M). Apoptosis was induced in MCF-7 and MCF-7s cells. In addition, extensive cytoplasmic vacuolation was observed, implying an incompleted autophagy as evidenced by the increase of autophagy-related proteins (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdc(scid)/J mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows cytotoxic activity on breast cancer both in vitro and in vivo. It seems to represent a robust promising agent for the treatment of breast cancer. Pristimerin's itself or synthetic novel derivatives should be taken into consideration for novel potent anticancer agent(s). (C) 2017 Elsevier Ltd. 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