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.

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)]·H2O (3), [Zn(5-FU)2(bpyma)]·2H2O (4) and [Zn(5-FU)2(terpy)]·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 γ-H2AX, thus contributing to its remarkable anticancer activity.

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)]·2DMF (Mn), [Fe(sac)2(H2O)(bzimpy)]·2H2O (Fe), [Co(bzimpy)2](sac)2·2H2O (Co), [Ni(bzimpy)2](sac)2·H2O·i-PrOH (Ni) and [Cu(sac)2(bzimpy)]·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 double-strand 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.

Correction: 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.

Correction for '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' by Ceyda Icsel et al., Dalton Trans., 2020, 49, 7842-7851, DOI: .

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)2·2H2O (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 vitro anticancer screening in A549 (lung), MCF-7 (breast) and HT29 (colon) cell lines showed that Zn was highly cytotoxic against A549 and MCF-7 cells with IC50 values of 1.74 ± 0.06 and 3.15 ± 0.10 µM, respectively, and Hg demonstrated potent cytotoxic activity in MCF-7 cells (8.61 ± 0.98 µM), while Cd and 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. Zn and Hg induced G0/G1 cell arrest and apoptotic cell death detected via typical 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).

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

New trans-[Pd(sac)2(PPhMe2)(DMSO)]·H2O (Pd) and trans-[Pt(sac)2(PPhMe2)2]·H2O (Pt) complexes (sac = saccharinate and PPhMe2 = 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.

Synthesis, characterization and crystal structures of platinum(II) saccharinate complexes with 1,5-cyclooctadiene.

Two new platinum(II) complexes, namely [PtCl(sac)(COD)] (1) and [Pt(sac)2(COD)] (2) (sac = saccharinate and COD = 1,5-cyclooctadiene), were synthesized and characterized by elemental analysis, IR, NMR, ESI-MS spectroscopic and thermal analysis (TG/DTA) methods. The platinum(II) complexes were prepared from the reaction of [PtCl2(COD)] with Na(sac)•2H2O. The addition of the sac ligand resulted in the replacement of 1 and 2 chlorido ligands in [PtCl2(COD)] to yield 1 and 2, respectively. The structures of the complexes were determined by single crystal X-ray diffraction and showed a distorted square planar coordination geometry around platinum(II). COD acted as a π-donor ligand, while sac was N -coordinated in both complexes. The TG/DTA data indicated that both complexes were thermally stable up to 220 °C in air and their thermal decompositions yielded Pt as a final product. Complexes 1 and 2 were also designed as possible precursors to synthesize new mixed-ligand platinum(II) sac complexes in a one-pot reaction.

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]·DMSO (1), cis-[Pt(sac)2(PPhMe2)2] (2), cis-[Pt(sac)2(PPh2Et)2] (3), and cis-[Pt(sac)2(PPhEt2)2]·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.

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.

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 = PdII (1, 3 and 5) and PtII (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/HSA 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 mitochondrial depolarization and DNA damage.

Palladium(ii) and platinum(ii) saccharinate complexes with bis(diphenylphosphino)methane/ethane: synthesis, S-phase arrest and ROS-mediated apoptosis in human colon cancer cells.

New neutral [M(sac)2(diphos)] and cationic [M(diphos)2](sac)2 complexes, where M = PdII or PtII, sac = saccharinate, and diphos = 1,1-bis(diphenylphosphino)methane (dppm) or 1,2-bis(diphenylphosphino)ethane (dppe), were synthesized and structurally characterized. The anticancer activity of the complexes was investigated against MCF-7 (breast), A549 (lung), HCT116 (colon), DU145 (prostate) cancer and BEAS-2B (normal bronchial epithelial) cells. Neutral Pt-dppm (2) and Pd-dppe complexes (5) did not show any biological activity. The cationic Pd-dppe (7) complex displayed antiproliferative activity, while the rest of the complexes exhibited potent cytotoxicity compared with cisplatin. The active Pd(ii)/Pt(ii) complexes were then included in further studies including interaction with DNA/HSA, nuclease activity, cellular uptake and lipophilicity. The potent complexes induced the apoptotic cell death as probed through annexin V positivity and caspase activation. Mechanistic studies on HCT116 cells showed that the complexes cause cell cycle arrest at the DNA synthesis (S) phase and excessive generation of reactive oxygen species (ROS), damaging to both mitochondria and DNA.

Synthesis, structures and anticancer potentials of platinum(II) saccharinate complexes of tertiary phosphines with phenyl and cyclohexyl groups targeting mitochondria and DNA.

A series of new Pt(II) saccharinate complexes containing PR3 ligands (PPh3, PPh2Cy, PPhCy2 and PCy3) with progressive phenyl (Ph) replacement by cyclohexyl (Cy) were synthesized and structurally characterized by IR, NMR, ESI-MS and X-ray diffraction. The anticancer activity of the complexes was tested against human breast (MCF-7), lung (A549), colon (HCT116), and prostate (DU145) cancer cell lines as well as against normal bronchial epithelial (BEAS-2B) cells. Trans-configured complexes 1, 3 and 5 emerged as potential anticancer drug candidates. The mechanism of action of the potent complexes was then investigated in detail. The three complexes interacted with DNA by groove binding and with HSA via hydrophobic IIA subdomain. Furthermore, the complexes cleaved plasmid DNA efficiently. Cellular uptake studies in MCF-7 cells showed that the biologically active complexes were mainly localized in cytoplasm. The cytotoxic activity was a function of the lipophilicity and cellular accumulation of the complexes. As determined by M30, Annexin V and Caspase 3/7 activity assays, the complexes induced apoptosis in MCF-7 and HCT116 cells. Mechanistic studies showed that the potent complexes cause excessive generation of reactive oxygen species (ROS) and display a dual action, concurrently targeting both mitochondria and genomic DNA.

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. [Ag2(barb)2(µ-dppm)2] (1), [Ag2(barb)2(µ-dppe)(DMSO)2] (2) and [Ag2(barb)2(µ-dppp)2] (3) were binuclear, while [Ag(barb)(µ-dppb)]n (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.

Synthesis, structures and biomolecular interactions of new silver(i) 5,5-diethylbarbiturate complexes of monophosphines targeting Gram-positive bacteria and breast cancer cells.

A series of new silver(i) 5,5-diethylbarbiturate (barb) complexes with the formulas [Ag2(µ-barb)2(PPh3)2] (1), [Ag(barb)(PPh2Cy)] (2), [Ag(barb)(PPhCy2)] (3) and [Ag(barb)(PCy3)] (4) (PPh3 = triphenylphosphine, PPh2Cy = diphenylcyclohexylphosphine, PPhCy2 = dicyclohexylphenylphosphine and PCy3 = tricyclohexylphosphine) were synthesized and fully characterized by elemental analysis, IR, NMR, ESI-MS and X-ray crystallography. All the complexes display a significant affinity towards DNA with a groove binding mode and also strongly bind to BSA via hydrophobic interactions. Lipophilicity increases from 1 to 4 with an increasing number of Cy groups in the phosphine ligands. Screening of the in vitro antimicrobial activity of 1-4 against the strains of Gram-negative (S. typhimurium ATCC 14028, E. coli ATCC 25922 and O157:H7) and Gram-positive (L. garvieae 40456, S. aureus ATCC 25923, and ATCC 33591) bacteria demonstrated that all the complexes exhibit very high activity and specific selectivity against the Gram-positive bacteria, compared to AgNO3 and silver sulfadiazine. Furthermore, the growth inhibitory effects of 1-4 on four human cancer cell lines (MCF-7, PC-3, A549 and HT-29) showed that 4 has a potent cytotoxic activity against MCF-7 cells, significantly higher than cisplatin and carboplatin. The effects of the complexes on the inhibition of the cells are closely related to their lipophilicity as well as DNA/protein binding. The induction of apoptosis of MCF-7 cells treated with 4 was probed through Hoechst 33342 staining, Annexin V positivity and caspase 3/7 activity. In addition, increased ROS levels in the presence of 4 are most likely responsible for damage to both mitochondria and genomic DNA.

A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer.

Recent accumulating evidence has supported the notion that tumors have hierarchically organized heterogeneous cell populations and a small subpopulation of cells, termed cancer stem cells (CSCs), are responsible for tumor initiation, maintenance as well as drug resistance. Therefore, targeting the CSCs along with the other cancer cells has been the most important topic during the last decade. In the present study, we evaluated the cytotoxic activity of trans-[PtCl2(2-hepy)2] [2-hepy=2-(2-hydroxyethyl) pyridine] complex and the mechanism of cell death in breast CSCs. Stemness markers, Oct-4 and Sox2, were determined in mammospheres by western blotting. Cytotoxicity was assessed using the ATP viability assay. Cell death was fluorescently visualized and further confirmed by flow cytometry as well as gene expression analysis. The Pt(II) complex significantly reduced the cell viability, prevented mammosphere formation and disrupted mammosphere structures in a dose-dependent manner (0-100µM). The mode of cell death was apoptosis and it was shown by the presence of caspase 3/7 activity, Annexin V-FITC positivity, decreased mitochondrial membrane potential and increased expressions of pro-apoptotic genes (TNFRSF10A and HRK). Interestingly, necroptosis was also observed by the evidence of increased MLKL expression. In conclusion, the Pt(II) complex seems to be a highly promising anticancer compound due to its promising cytotoxic activity on CSCs. Therefore, it deserves in vivo further studies for the proof-of-concept.

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-κN,N')3]Cl(barb)·7H2O (), [Cu(barb-κN)(barb-κ(2)N,O)(phen-κN,N')]·H2O (), [Cu(barb-κN)2(phen-κN,N')] (), [Zn(barb-κN)2(phen-κN,N')]·H2O (), [Ni(barb-κ(2)N,O)(dpya-κN,N')2]Cl·2H2O (), [Cu(barb-κ(2)N,O)2(dpya-κN,N')]·2H2O () and [Zn(barb-κN)2(dpya-κN,N')] (), 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, and 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 exhibited the highest affinity towards DNA and BSA. Enzyme inhibition assay showed that show a preference for both A/T and G/C rich sequences in pUC19 DNA, while and 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 was deposited mostly in the membrane fraction of the cells. Among the present complexes, exhibited a very strong cytotoxic effect on A549, MCF-7, HT-29 and DU-145 cancer cells, being more potent than cisplatin. Moreover, induces cell death through the apoptotic mode obtained by flow cytometry.

Cationic Pd(II)/Pt(II) 5,5-diethylbarbiturate complexes with bis(2-pyridylmethyl)amine and terpyridine: Synthesis, structures,DNA/BSA interactions, intracellular distribution, cytotoxic activity and induction of apoptosis.

Four new cationic Pd(II) and Pt(II) 5,5-diethylbarbiturate (barb) complexes, [M(barb)(bpma)]X·H2O [M = Pd(II), X = Cl (1); M = Pt(II), X = NO3(-) (2)] and [M(barb)(terpy)]NO3·0.5H2O [M = Pd(II) (3); M = Pt(II) (4)], where bpma = bis(2-pyridylmethyl)amine and terpy = terpyridine, were synthesized and characterized by elemental analysis, IR, UV­vis, NMR, ESI-MS and X-ray crystallography. The DNA binding properties of the cationic complexes were investigated by spectroscopic titrations, displacement experiments, viscosity, DNA melting and electrophoresis measurements. The results revealed that the complexes effectively bind to FS-DNA (fish sperm DNA) via intercalative/minor groove binding modes with intrinsic binding constants (Kb) in the range of 0.50 × 10(4)­1.67 × 10(5) M(-1). Absorption, emission and synchronous fluorescence measurements showed strong association of the complexes with protein (BSA) through a static mechanism. The mode of interaction of complexes towards DNA and protein was also supported by molecular docking. Complexes 1 and 3 showed significant nuclear uptake in HT-29 cells. In addition, 1 and 3 showed higher inhibition than cisplatin on the growth of MCF-7 and HT-29 cells and induced apoptosis on these cells much more effectively than the rest of the complexes as evidenced by pyknotic nuclear morphology. The levels of caspase-cleaved cytokeratin 18 (M30 antigen) in HT-29 cells treated with 1 and 3 increased in a dose-dependent manner, suggesting apoptosis. Moreover, qRT-PCR experiments showed that 1 and 3 caused significant increases in the expression of TNFRSF10B in HT-29 cells, indicating the initiation of apoptosis via cell surface death receptors.

Anti-growth effect of a novel trans-dichloridobis[2-(2-hydroxyethyl)pyridine]platinum (II) complex via induction of apoptosis on breast cancer cell lines.

Breast cancer still continues to be the leading cause of cancer-related mortality in women worldwide. Although advances have been made in the treatment of this disease during the past decade, new approaches and novel compounds are urgently needed. The aim of this study was to evaluate the cytotoxic activity of trans-[PtCl2(2-hepy)2] [2-hepy=2-(2-hydroxyethyl) pyridine] on breast cancer cell lines, MCF-7 and MDA-MB-231. The platinum (II) complex was synthesized and characterized by our laboratory working group. Anti-growth effect was assayed by the MTT and ATP viability assays and also monitored real-time using xCELLigence system. The mode of cell death was evaluated by using the fluorescence microscopy (Hoechst 33342+Calcein-AM+Propidium iodide staining), Western blotting (cleaved PARP and caspase 3, total caspase 8), flow cytometry (quantitative analysis of live, early/late apoptotic, dead cells and caspase 3/7 activity) and the RT-PCR (the genes analyzed were BCL-2L10, BIK, BAX, BCL-2, FASLG, HRK, TNFRSF10B, and TNFRSF10A). The platinum (II) complex had anti-growth effect in a dose dependent manner in vitro. Cells were killed by apoptosis as evidenced by the pyknotic nuclei, cleavage of poly-(ADP-ribose) polymerase (PARP) and induction of active caspase-3. These results suggest that the complex might represent a potentially active novel drug for the breast cancer treatment and warrants further studies due to its promising cytotoxic activity.

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.

Novel palladium(ii) and platinum(ii) complexes of 5,5-diethylbarbiturate (barb) with 2-phenylpyridine (Hppy), 2,2'-bipyridine (bpy) and 2,2'-dipyridylamine (dpya) have been prepared and characterized by elemental analysis, IR, UV-Vis, NMR and ESI-MS. Single-crystal diffraction measurements show that complex consists of binuclear [Pd2(µ-barb-κN,O)2(ppy-κN,C)2] moieties, while complexes are mononuclear, [M(barb-κN)2(L-κN,N')] (L = bpy or dpya). has a composition of [Pt(dpya-κN,N')2][Ag(barb-κN)2]2·4H2O and was assumed to have a structure of [Pt(barb-κN)(Hppy-κN)(ppy-κN,C)]·3H2O. The complexes were found to exhibit significant DNA binding affinity by a non-covalent binding mode, in accordance with molecular docking studies. In addition, complexes and displayed strong binding with supercoiled pUC19 plasmid DNA. Cellular uptake studies were performed to assess the subcellular localization of the selected complexes. A moderate radical scavenging activity of and was confirmed by DPPH and ABTS tests. Complexes , , and showed selectivity against HT-29 (colon) cell line.

A combined experimental and theoretical investigation of a new imineoxime and its palladium(II) and platinum(II) complexes: synthesis, structural characterization and spectroscopic properties.

A new imineoxime compound {(1E,2E)-(2-hydroxy-ethylimino)-naphthalene-2yl-ethanal oxime (heineoH)} and its palladium(II) and platinum(II) complexes ([M(heineo)2]) have been synthesized and characterized by IR, NMR, UV-vis, elemental analysis, mass spectra and X-ray single crystal diffraction. [Pt(heineo)2] was obtained as a single crystal, while [Pd(heineo)2] was synthesized as a polycrystalline powder. The X-ray diffraction analysis of the [Pt(heineo)2] indicated that the platinum(II) ion is coordinated by two heineo ligands in a distorted square-planar geometry. DFT (B3LYP/6-311++G(d,p) and LANL2DZ) calculations on the ligand and its complexes were carried out to correlate the geometry and vibrational and electronic properties. Additionally, heineoH is fluorescent in EtOH at room temperature, but the fluorescence is quenched in the case of the metal complexes.