title: DNA condensation by copper(II) complexes and their anti-proliferative effect on cancerous and normal fibroblast cells.
abstract: In our search towards copper(II) based anticancer compounds, copper(II) complexes [Cu(bitpy)2](ClO4)21, [Cu(bitpy)(phen)](NO3)22 and [Cu(bitpy)(NO3)](NO3) 3 were synthesized and characterized. All the three complexes contain the tridentate ligand bitpy, which bears biologically relevant benzimidazolyl head group, as one of the ligands. Because of the presence of the planar benzimidazolyl group in the bitpy ligand, the complexes exhibited intercalative mode of binding with DNA. The DNA binding constant, K(b), for complexes 1, 2 and 3 were determined to be (1.84 ± 0.32) × 10(4), (1.83 ± 0.57) × 10(4) and (1.87 ± 0.21) × 10(4) M(-1) respectively. All the three complexes possessed DNA condensing ability. The DNA condensing ability of the complexes was in the order 2 > 1 > 3. The DNA condensation induced by these three complexes was found to be reversed in the presence of 1 M NaCl. In vitro cytotoxicity of three complexes was tested against osteosarcoma MG63 cell line as well as normal fibroblast NIH3T3 cell line by MTT reduction assay. Complexes 1 and 2 were found to be highly toxic towards MG63 than NIH3T3 cell line and both these complexes brought about cell death in the MG-63 cell line due to apoptosis. Whereas, complex 3 exhibited almost equal toxic effect towards both MG63 and NIH3T3 cell lines. Based on the fact that both complexes 1 and 2 brought about reversible condensation of DNA and induced apoptosis in osteosarcoma MG-63 cell line, it is hypothesized that they might possess potential pharmaceutical applications.
authors.affiliation: Chemical Laboratory, Central Leather Research Institute, Council of Scientific and Industrial Research, Adyar, Chennai 600 020, India.
authors.forename: Subramaniyam
authors.initials: S
authors.lastname: Rajalakshmi
authors.affiliation: Bio-Materials Laboratory, Central Leather Research Institute, Council of Scientific and Industrial Research, Adyar, Chennai 600 020, India.
authors.forename: Manikantan Syamala
authors.initials: MS
authors.lastname: Kiran
authors.affiliation: Chemical Laboratory, Central Leather Research Institute, Council of Scientific and Industrial Research, Adyar, Chennai 600 020, India. Electronic address: bunair@clri.res.in.
authors.forename: Balachandran Unni
authors.initials: BU
authors.lastname: Nair
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D041681:NIH 3T3 Cells
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003300:Copper; D004247:DNA
keywords: Apoptosis; Copper(II) complexes; DNA condensation; MG63 fibroblast cell; Mitochondrial pathway; Oxidative stress