1357565-67-3Relevant academic research and scientific papers
TCM active ingredient oxoglaucine metal complexes: Crystal structure, cytotoxicity, and interaction with DNA
Chen, Zhen-Feng,Shi, Yan-Fang,Liu, Yan-Cheng,Hong, Xue,Geng, Bo,Peng, Yan,Liang, Hong
, p. 1998 - 2009 (2012)
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][AuCl4]·DMSO (1), [Zn(OG)2(H 2O)2]- (NO3)2 (2), [Co(OG) 2(H2O)2](ClO4)2 (3), and [Mn- (OG)2(H2O)2](ClO4)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 [AuCl4] -. 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 NO3- or ClO4 - 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 IC5 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.
