title: Spectroscopy, cytotoxicity and DNA-binding of the lanthanum(III) complex of an L-valine derivative of 1,10-phenanthroline.
abstract: The interaction of the lanthanum(III) La(III)-L (L=N,N'-bis-(1-carboxy-2-methylpropyl)-1,10-phenanthroline-2,9-dimethanamine) complex with calf thymus DNA was studied by electronic spectra, fluorescence spectra and circular dichroic spectra. The La(III)-L complex was assayed for antitumor activity in vitro against the HL-60 (the human leucocytoma) cells, HCT-8 (the human coloadenocarcinoma) cells, BGC-823 (the human carcinoma of stomach) cells, Bel-7402 (the human liver carcinoma) cells and KB (the human nasopharyngeal carcinoma) cells. The results show that the La(III)-L complex has activity against HL-60 cells, Bel-7402 cells and KB cells. Moreover, it is slightly more effective against Bel-7402 cell line than cisplatin. Using ethidium bromide as a fluorescence probe, the binding mode of the La(III)-L complex to calf-thymus DNA was studied spectroscopically. For comparison, the same measurements were carried out with La(III)-Phen [La(III)-1,10-phenanthroline complex] and La(III)-Val [La(III)-L-valine complex]. The results indicate that the La(III)-L and La(III)-Phen complexes possibly interact with calf-thymus DNA by both intercalative and coordination binding, whereas the La(III)-Val complex interacts with calf-thymus DNA by coordination binding. Kinetics of binding of the three complexes to DNA is for the first time studied using ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer under pseudo-first-order condition. The strong two-step mechanisms in the process of the La(III)-L and La(III)-Phen complexes and one step in the process of the complex La(III)-Val interacting with DNA are observed, and the k(obs) (observed pseudo-first-order rate constant) and E(a) (observed energy of activation) values of binding to DNA are obtained.
authors.affiliation: Department of Chemistry, Nankai University, 300071, Tianjin, PR China.
authors.forename: Zhong Ming
authors.initials: ZM
authors.lastname: Wang
authors.forename: Hua Kuan
authors.initials: HK
authors.lastname: Lin
authors.forename: Shou Rong
authors.initials: SR
authors.lastname: Zhu
authors.forename: Tian Fu
authors.initials: TF
authors.lastname: Liu
authors.forename: Yun Ti
authors.initials: YT
authors.lastname: Chen
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007811:Lanthanum / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D013054:Spectrophotometry, Atomic; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014633:Valine / Q000737:chemistry*
chemical_list: D010618:Phenanthrolines; D007811:Lanthanum; D004247:DNA; D014633:Valine; C025205:1,10-phenanthroline