Büyükgüngör, Orhan2024-05-282024-05-282015-110162-0134https://www.sciencedirect.com/science/article/pii/S0162013415300714https://hdl.handle.net/11452/41536Four new cationic Pd(II) and Pt(II) 5,5-diethylbarbiturate (barb) complexes, [M(barb)(bpma)]X center dot H2O [M = pd(II), X = Cl (1); M = Pt-II, X = NO3- (2)] and [M(barb)(terPY)]NO3 center dot 0.5H(2)O [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, UV-vis, 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 x 10(4) - 1.67 x 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 I and 3 caused significant increases in the expression of TNFRSF10B in HT-29 cells, indicating the initiation of apoptosis via cell surface death receptors.eninfo:eu-repo/semantics/closedAccessAnticancer activityDNA/BSA bindingElectrophoresisNuclear uptakePd(II)/Pt(II) 5,5-Diethylbarbiturate complexesHuman serum-albuminIntrastrand cross-linkDna dodecamer duplexCells in-vitroCrystal-structurePlatinum(II) complexesCoordination-compoundsBiological evaluationAnticancer activityMolecular dockingBiochemistry & molecular biologyChemistryAmino acid sequenceAntineoplastic agentsApoptosisBarbituratesBase sequenceDNAHT29 cellsHumansMCF-7 cellsMolecular docking simulationMolecular sequence dataOrganoplatinum compoundsPalladiumProtein bindingPyridinesSerum albumin, bovineArticle0003671278000042-s2.0-849405396253852152Special Issue26339715https://doi.org/10.1016/j.jinorgbio.2015.08.026Biochemistry & molecular biologyChemistry, inorganic & nuclearSubstitution Reaction; Nucleophile; PalladiumAntineoplastic metal complexBis(2 pyridylmethyl)amineBovine serum albuminCisplatinCytokeratin 18DeoxyribonucleaseDNAFas antigenHydrogenPalladiumPhosphatidylinositol 3,4,5 trisphosphate 3 phosphatasePlasmid DNAPlatinumProtein kinase BTerpyridineUnclassified drugAntineoplastic agentBarbituric acid derivativeN,N-bis(2-pyridylmethyl)aminePalladiumPlatinum complexProtein bindingPyridine derivative