title: Synthesis, characterization, and in vitro antitumor properties of gold(III) compounds with the traditional Chinese medicine (TCM) active ingredient liriodenine.
abstract: Liriodenine, an oxoaporphine alkaloid with anticancer activity isolated from Zanthoxylum nitidum (rutaceous anticancer traditional Chinese medicine), was selected as a bioactive ligand to react with HAuCl(4) and NaAuCl(4) to afford [LH][AuCl(4)] (1) and [AuCl(3)L] (2), respectively (where L is liriodenine). The structures of 1 and 2 were characterized by IR spectroscopy, electrospray ionization mass spectrometry, (1)H-NMR spectroscopy, and elemental analysis. The single-crystal X-ray diffraction analysis of 1 revealed that it is an ionic compound consisting of protonated liriodenine cation [LH](+) and [AuCl(4)](-) anion. The spectroscopic analysis showed that 2 is a coordination compound, in which one liriodenine coordinates to gold via its 7-N donor. In aqueous solution, 1 is relatively stable, but 2 undergoes rapid hydrolysis. The in vitro cytotoxicity towards five human tumor cell lines shows that 1 and 2 manifest roughly similar biological behavior and appreciable antiproliferative properties, with IC(50) values falling in the 2-16 μM range. The flow-cytometric analysis of 1 and 2 suggests that both compounds induced an S-phase arrest. Compounds 1 and 2 significantly poison topoisomerase I in vitro at low concentration (25 μM or less). DNA binding studies indicate that both 1 and 2 interact with DNA mainly via intercalation between the neighboring base pairs of the DNA double helix. Electrostatic interactions of 1 and 2 with the polyanionic DNA phosphate backbone may reinforce the intercalation because both 1 and 2 are composed of planar cationic species.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Chemical Engineering of Guangxi Normal University, Guilin, 541004, People's Republic of China. chenzfubc@yahoo.com
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Xue
authors.initials: X
authors.lastname: Hong
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Wang
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001060:Aporphines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008516:Medicine, Chinese Traditional; D009369:Neoplasms / Q000188:drug therapy; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D032106:Zanthoxylum / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001060:Aporphines; D007364:Intercalating Agents; D050607:Organogold Compounds; D004247:DNA; C026980:liriodenine