Divalent later transition metal complexes of the traditional chinese medicine (TCM) liriodenine: coordination chemistry, cytotoxicity and DNA binding studies.
Liriodenine (L), a natural alkaloid, was isolated as an active component from the anticancer traditional Chinese medicine (TCM), Zanthoxylum nitidum. It reacted with Mn(II), Fe(II), Co(II) and Zn(II) to afford four metal complexes: [MnCl(2)(L)(2)] (1), [FeCl(2)(L)(2)] (2), [Co(L)(2)(H(2)O)(2).Co(L)(2)(CH(3)CH(2)OH)(2)](ClO(4))(4) (3), and [Zn(2)(L)(2)(mu(2)-Cl)(2)Cl(2)] (4), which were characterized by elemental analysis, IR, ESI-MS. Their crystal structures were determined by the single crystal X-ray diffraction method. The in vitro cytotoxicity of L and complexes 1-4 against 10 human tumour cell lines was assayed. Some of these metal-based compounds exhibited enhanced cytotoxicity vs. free L to selected tumour cell lines. The binding properties of L and its complexes 1-4 to ct-DNA were investigated by spectroscopic methods and viscosity measurements. Agarose gel electrophoresis experiments were also carried out to evaluate their unwinding ability towards plasmid DNA and their inhibition towards Topoisomerase I. All the results indicate that complexes 1-4 may bind more intensively to the DNA helix than does L, and intercalative binding for complexes 1-4 and electrostatic interactions for complexes 3-4 to DNA should be considered. For complex 4, covalent binding to DNA may exist. Of special note, all these metal complexes effectively inhibit Topoisomerase I even at low concentration (< or = 10 microM).
Liu
Yan-Cheng
YC
Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin, 541004, P. R. China.
Chen
Zhen-Feng
ZF
Liu
Li-Min
LM
Peng
Yan
Y
Hong
Xue
X
Yang
Bin
B
Liu
Hua-Gang
HG
Liang
Hong
H
Orvig
Chris
C
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001060:Aporphines / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008516:Medicine, Chinese Traditional; D008968:Molecular Conformation; D059004:Topoisomerase I Inhibitors; D032106:Zanthoxylum / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D056831:Coordination Complexes; D059004:Topoisomerase I Inhibitors; D004247:DNA; C026980:liriodenine; D004264:DNA Topoisomerases, Type I