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Synthesis, characterization, and in vitro antitumor properties of gold(III) compounds with the traditional Chinese medicine (TCM) active ingredient liriodenine.
- Source :
-
Journal of Biological Inorganic Chemistry (JBIC) . Feb2012, Vol. 17 Issue 2, p247-261. 15p. 3 Color Photographs, 2 Diagrams, 5 Charts, 5 Graphs. - Publication Year :
- 2012
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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]
Details
- Language :
- English
- ISSN :
- 09498257
- Volume :
- 17
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Inorganic Chemistry (JBIC)
- Publication Type :
- Academic Journal
- Accession number :
- 71107689
- Full Text :
- https://doi.org/10.1007/s00775-011-0846-z