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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]

Abstract: Three new compounds of Ga(III), Au(III), Sn(IV) with matrine (MT), [H-MT][GaCl4] ( 1 ), [H-MT][AuCl4] ( 2 ) and [Sn(H-MT)Cl5] ( 3 ), have been synthesized and characterized by elemental analysis, IR, ESI-MS and single crystal X-ray diffraction methods. The crystal structural analyses indicate that 1 and 2 are ionic compounds, whereas 3 is a tin(IV) complex formed by the monodentate MT via its carbonyl oxygen atom of MT coordinating to Sn(IV). Their in vitro cytotoxicity towards eight selected tumour cell lines has been evaluated by MTT (3-[4,5-Dimentylthiazole-2-yl]-2,5-diphenpyltetra-zolium bromide) method, and compounds 1 and 2 exhibit enhanced activity, such as 1 to SW480, 2 to HeLa, HepG2 and MCF-7, which exceeds matrine and cisplatin, and display synergistic contribution of their components. The cell cycle analyses show that compounds 1 , 3 and MT exhibit cell cycle arrest at the G2/M phase. Interactions of these compounds with calf thymus DNA (ct-DNA) have been investigated by spectroscopic analyses. The planar extension of the intercalative metal–matrine compounds increases the interaction of the metal–matrine with DNA, indicating that the cationic metal ions and configuration of the intercalated metal–matrine will affect the extent of interaction. Compound 2 , [H-MT][AuCl4], exhibits more intensive binding ability to DNA, which may correlate with intercalation and other action mode. The circular dichroism spectra of the ct-DNA bound with metal–MT compounds also suggest that ct-DNA interacted with 1 , 2 , 3 does not influence its secondary structure. Furthermore, both compounds 1 and 2 exhibit effective inhibition ability to topoisomerase (TOPO I) at concentration of 50μM, while matrine and compound 3 do not. [ABSTRACT FROM AUTHOR]