High cytotoxicity of dihalo-substituted 8-quinolinolato-lanthanides.
Three new lanthanide complexes with dihalo-substituted 8-quinolinol: [Gd(BrQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (1), [Dy(ClQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (2), [Er(ClQ)(3)(H(2)O)(2)]·1.33EtOH·0.33H(2)O (3) (H-BrQ = 5,7-dibromo-8-quinolinol, H-ClQ = 5,7-dichloro-8-quinolinol) have been synthesized and characterized by elemental analysis, IR, ESI-MS, single-crystal X-ray diffraction and TGA. The single-crystal X-ray diffraction analyses reveal that complexes 1-3 are mononuclear and isostructural. Each metal centre is coordinated by three dihalo-substituted 8-quinolinol and two aqua ligands. The in vitro cytotoxicity of dihalo-substituted 8-quinolinol and complexes 1-3 against liver cancer BEL7404 was evaluated. The IC(50) values of 1-3 to BEL7404 were 47.2 ± 2.6, 18.3 ± 1.0 and 31.5 ± 1.2 nM, respectively. The lanthanide complexes 1-3 exhibited significantly enhanced cytotoxicity vs. free substituted 8-quinolinol. The binding properties of dihalo-substituted 8-quinolinol and complexes 1 and 2 to DNA were investigated by UV-vis, fluorescence, CD spectroscopy and viscosity measurements, as well as agarose gel electrophoresis experiments. Both complexes 1 and 2 interact more strongly with DNA than the free quinolinol ligand. Intercalation is the most probable binding mode for both the complexes and the quinolinol ligands.
Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Education China, School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, PR China. chenzfubc@yahoo.com
Zhen-Feng
ZF
Chen
Xiao-Yan
XY
Song
Yan
Y
Peng
Xue
X
Hong
Yan-Cheng
YC
Liu
Hong
H
Liang
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D006801:Humans; D028581:Lanthanoid Series Elements / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy; D008958:Models, Molecular; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013053:Spectrophotometry
D000970:Antineoplastic Agents; D003603:Cytotoxins; D028581:Lanthanoid Series Elements; D011804:Quinolines; D004247:DNA; C427203:calf thymus DNA