1. Synthesis, characterization, and in vitro antitumor properties of gold(III) compounds with the traditional Chinese medicine (TCM) active ingredient liriodenine.
- Author
-
Chen, Zhen-Feng, Liu, Yan-Cheng, Peng, Yan, Hong, Xue, Wang, Hong-Hong, Zhang, Min-Min, and Liang, Hong
- Subjects
- *
ANTINEOPLASTIC agents , *GOLD compounds , *CHINESE medicine , *BIOACTIVE compounds , *DNA topoisomerase I , *CELL-mediated cytotoxicity , *DNA-ligand interactions , *CANCER cells , *X-ray crystallography ,THERAPEUTIC use of alkaloids - 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 and NaAuCl to afford [LH][AuCl] ( 1) and [AuClL] ( 2), respectively (where L is liriodenine). The structures of 1 and 2 were characterized by IR spectroscopy, electrospray ionization mass spectrometry, 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] 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 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. Graphical abstract: Two liriodenine (L) gold(III) compounds [LH][AuCl] ( 1) and [AuClL] ( 2) were synthesized. The in vitro cytotoxicity towards five human tumor cell lines was tested and shows that 1 and 2 manifest appreciable antiproliferative properties, with IC values falling in the 2-16 μM range. Both 1 and 2 interact with DNA mainly via an intercalation mode, but electrostatic binding may exist. They both inhibit topoisomerase I activity at low concentration (25 μM or less). [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF