Spectroscopy, cytotoxicity and DNA-binding of the lanthanum(III) complex of an L-valine derivative of 1,10-phenanthroline.
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.
Wang
Zhong Ming
ZM
Department of Chemistry, Nankai University, 300071, Tianjin, PR China.
Lin
Hua Kuan
HK
Zhu
Shou Rong
SR
Liu
Tian Fu
TF
Chen
Yun Ti
YT
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*
D010618:Phenanthrolines; D007811:Lanthanum; D004247:DNA; D014633:Valine; C025205:1,10-phenanthroline