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Divalent later transition metal complexes of the traditional chinese medicine (TCM) liriodenine: coordination chemistry, cytotoxicity and DNA binding studies

TitleDivalent later transition metal complexes of the traditional chinese medicine (TCM) liriodenine: coordination chemistry, cytotoxicity and DNA binding studies
Publication TypeJournal Article
Year of Publication2009
AuthorsLiu, YC, Chen, ZF, Liu, LM, Peng, Y, Hong, X, Yang, B, Liu, HG, Liang, H, Orvig, C
JournalDalton Transactions
Pagination10813-10823
Type of ArticleArticle
ISBN Number1477-9226
Keywordsantitumor agents, CISPLATIN, CRYSTAL-STRUCTURE, GEL-ELECTROPHORESIS, INHIBITION, INNOVATIVE COMBINATION, INTERCALATION, PLATINUM ANTICANCER AGENTS, RUTHENIUM(II) COMPLEXES, TOPOISOMERASE-I
Abstract

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: [MnCl2(L)(2)] (1), [FeCl2(L)(2)] (2), [Co(L)(2)(H2O)(2)center dot Co(L)(2)(CH3CH2OH)(2)](ClO4)(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 (<= 10 mu M).

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