TCM active ingredient oxoglaucine metal complexes: crystal structure, cytotoxicity, and interaction with DNA

Inorg Chem. 2012 Feb 20;51(4):1998-2009. doi: 10.1021/ic200443p. Epub 2012 Feb 6.


The alkaloid oxoglaucine (OG), which is a bioactive component from traditional Chinese medicine (TCM), was synthesized by a two-step reaction and used as the ligand to react with transition metal salts to give four complexes: [OGH][AuCl(4)]·DMSO (1), [Zn(OG)(2)(H(2)O)(2)](NO(3))(2) (2), [Co(OG)(2)(H(2)O)(2)](ClO(4))(2) (3), and [Mn(OG)(2)(H(2)O)(2)](ClO(4))(2) (4). The crystal structures of the metal complexes were confirmed by single crystal X-ray diffraction. Complex 1 is an ionic compound consisting of a charged ligand [OGH](+) and a gold complex [AuCl(4)](-). Complexes 2-4 all have similar structures (inner-spheres), that is, octahedral geometry with two OG coordinating to one metal center and two aqua ligands occupying the two apical positions of the octahedron, and two NO(3)(-) or ClO(4)(-) as counteranions in the outer-sphere. The complexation of OG to metal ion was confirmed by ESI-MS, capillary electrophoresis and fluorescence polarization. The in vitro cytotoxicity of these complexes toward a various tumor cell lines was assayed by the MTT method. The results showed that most of these metal-oxoglaucine complexes exhibited enhanced cytotoxicity compared with oxoglaucine and the corresponding metal salts, with IC(50) values ranging from 1.4 to 32.7 μM for sensitive cancer cells, which clearly implied a positive synergistic effect. Moreover, these complexes appeared to be selectively active against certain cell lines. The interactions of oxoglaucine and its metal complexes with DNA and topoisomerase I were investigated by UV-vis, fluorescence, CD spectroscopy, viscosity, and agarose gel electrophoresis, and the results indicated that these OG-metal complexes interact with DNA mainly via intercalation. Complexes 2-4 are metallointercalators, but complex 1 is not. These metal complexes could effectively inhibit topoisomerase I even at low concentration. Cell cycle analysis revealed that 1-3 caused S-phase cell arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apomorphine / analogs & derivatives*
  • Apomorphine / chemistry
  • Apomorphine / pharmacology
  • Cattle
  • Cell Cycle / drug effects
  • Cell Line
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • DNA / metabolism
  • DNA Topoisomerases, Type I / metabolism
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology
  • Transition Elements / chemistry
  • Transition Elements / pharmacology


  • Antineoplastic Agents, Phytogenic
  • Coordination Complexes
  • Drugs, Chinese Herbal
  • Topoisomerase I Inhibitors
  • Transition Elements
  • oxoglaucine
  • DNA
  • calf thymus DNA
  • DNA Topoisomerases, Type I
  • Apomorphine