期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 103, 期 10, 页码 1405-1414出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2009.08.003
关键词
Iridium; Bis-intercalation; Polypyridyl ligands; Cytotoxicity; Cellular uptake; DNA binding
资金
- Deutsche Forschungsgemeinschaft (DFG)
The DNA binding and in vitro cytotoxicity of the dinuclear Ir(III) polypyridyl complexes [{(eta(5)-C5Me5) Ir(dppz)}(2)(mu-pyz)](CF3SO3)(4) 1 and [{(eta(5)-C5Me5)Ir(pp)}(2)(mu-4,4'-bpy)](CF3SO3)(4) 2-4 (pp = dipyrido[3,2-d: 2',3'-f]quinoxaline (dpq), dipyrido[2,3-a:2',3'-c]phenazine (dppz), benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn)) with the rigid bridging ligands pyrazine (pyz) or 4,4'-bipyridine (4,4'-bpy) have been studied. Stable intercalative binding into CT DNA (calf thymus DNA) is indicated for the dppz complexes 1 and 3 by induced negative CD bands at about 300 nm and large viscosity increases, with the individual measurements being in accordance with intrastrand bis-intercalation for 3 and mono-intercalation for 1. The observed interruption of specific interresidue NOE cross peaks from the relevant nucleobase H6/H8 protons to the sugar H2'/H2 '' protons of the preceding nucleotide is in accordance with bis-intercalation of complex 3 between the C3G18 and G4C17 base pairs and the T5A16 and A6T15 base pairs of the decanucleotide d(5'-CGCGTAGGCC-3'). Complexes I and 3 exhibit a greatly improved uptake by HT-29 (colon carcinoma) cells and significantly improved in vitro IC50 values of 1.8 +/- 0.1 and 3.8 +/- 0.1 mu M towards this cell line in comparison to the mononuclear complex [(eta(5)-C5Me5)IrCl(dppz)](CF3SO3) (IC50 = 7.4 +/- 0.9 mu M). (C) 2009 Elsevier Inc. All rights reserved.
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