title: Potential new inorganic antitumour agents from combining the anticancer traditional Chinese medicine (TCM) matrine with Ga(III), Au(III), Sn(IV) ions, and DNA binding studies.
abstract: Three new compounds of Ga(III), Au(III), Sn(IV) with matrine (MT), [H-MT][GaCl(4)] (1), [H-MT][AuCl(4)] (2) and [Sn(H-MT)Cl(5)] (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 G(2)/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][AuCl(4)], 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 50 μM, while matrine and compound 3 do not.
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, PR China. chenzfubc@yahoo.com
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Mao
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Liu
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: Hua-Gang
authors.initials: HG
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D005708:Gallium; D006046:Gold; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014001:Tin; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004365:Drugs, Chinese Herbal; D011807:Quinolizines; D059003:Topoisomerase Inhibitors; D014001:Tin; D006046:Gold; D004247:DNA; C427203:calf thymus DNA; D005708:Gallium; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D000093842:Matrines