title: Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand.
abstract: A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1½H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24 h. Positive-ion ESI-MS spectra show existence of only undissociated [Cu(phen)(aa)](+) species. Electron paramagnetic resonance, gel electrophoresis, fluorescence quenching, and restriction enzyme inhibition assay were used to study the binding interaction, binding affinity and selectivity of these complexes for various types of B-form DNA duplexes and G-quadruplex. All complexes can bind selectively to DNA by intercalation and electrostatic forces, and inhibit topoisomerase I. The effect of the methyl substituents of the coordinated amino acid in the above complexes on these biological properties are presented and discussed. The IC(50) values (24 h) of 1-4 for nasopharyngeal cancer cell line HK1 are in the range 2.2-5.2 μM while the corresponding values for normal cell line NP69 are greater than 13.0 μM. All complexes, at 5 μM, induced 41-60 % apoptotic cell death in HK1 cells but no significant cell death in NP69 cells.
authors: Unit GL33, Malaysia University of Science and Technology, 47301, Petaling Jaya, Malaysia.
authors: Hoi-Ling
authors: HL
authors: Seng
authors: Wai-San
authors: WS
authors: Wang
authors: Siew-Ming
authors: SM
authors: Kong
authors: Han-Kiat
authors: HK
authors: Alan Ong
authors: Yip-Foo
authors: YF
authors: Win
authors: Raja Noor Zaliha
authors: RN
authors: Raja Abd Rahman
authors: Makoto
authors: M
authors: Chikira
authors: Weng-Kee
authors: WK
authors: Leong
authors: Munirah
authors: M
authors: Ahmad
authors: Alan Soo-Beng
authors: AS
authors: Khoo
authors: Chew-Hee
authors: CH
authors: Ng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D059004:Topoisomerase I Inhibitors; D003300:Copper; D004247:DNA; D005998:Glycine