title: Synthesis, characterization, interaction with DNA, and cytotoxic effect in vitro of new mono- and dinuclear Pd(II) and Pt(II) complexes with benzo[d]thiazol-2-amine as the primary ligand.
abstract: A series of novel Pd(II) and Pt(II) complexes, [PdL(2)Cl(2)]·DMF (1), [Pd(2)(L-H)(2)(bpy)Cl(2)]·(H(2)O)(2)·DMF (2), [Pd(2)(L-H)(2)(phen)Cl(2)]·2H(2)O (3), [PtL(2)Cl(2)]·H(2)O (4), [Pt(2)(L-H)(2)(bpy)Cl(2)]·2H(2)O (5), and [Pt(2)(L-H)(2)(phen)Cl(2)]·H(2)O (6), where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and L = 1,3-benzothiazol-2-amine, have been synthesized and characterized. The competitive binding of the complexes to DNA has been investigated by fluorescence spectroscopy. The values of the apparent DNA binding constant, calculated from fluorescence spectral studies, were 3.8 × 10(6) (K(app)(4)), 2.9 × 10(6) (K(app)(1)), 2.4 × 10(6) (K(app)(6)), 2.0 × 10(6) (K(app)(5)), 1.2 × 10(6) (K(app)(3)), and 6.9 × 10(5) (K(app)(2)). The binding parameters for the fluorescence Scatchard plot were also determined. On the basis of the data obtained, it indicates that the six complexes bind to DNA with different binding affinities in the relative order 4 > 1 > 6 > 5 > 3 > 2. Viscosity studies carried out on the interaction of complexes with Fish Sperm DNA (FS-DNA) suggested that all complexes bind by intercalation. Gel electrophoresis assay demonstrates that all the complexes can cleave the pBR 322 plasmid DNA and bind to DNA in a similar mode. The cytotoxic activity of the complexes has been also tested against four different cancer cell lines. The results show that all complexes have activity against KB, AGZY-83a, Hep-G2, and HeLa cells. In general, the Pt(II) complexes were found to be more effective than the isostructural Pd(II) complexes. The mononuclear complexes exhibited excellent activity in comparison with the dinuclear complexes in these four cell lines. Moreover, on the KB cell line (the human oral epithelial carcinoma), the observed result seems quite encouraging for the six complexes with IC(50) values ranging from 1.5 to 8.6 μM. Furthermore, apoptosis assay with hematoxylin-eosin staining shows treatment with the six complexes results in morphological changes of KB cells. The results induce apoptosis in KB cells.
authors.affiliation: Department of Coordination Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China. ejgao@yahoo.com.cn
authors.forename: EnJun
authors.initials: E
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: MingChang
authors.initials: M
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Guan
authors.forename: XiaNan
authors.initials: X
authors.lastname: Gao
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: WanZhong
authors.initials: W
authors.lastname: Zhang
authors.forename: YaGuang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005399:Fishes; D006367:HeLa Cells; D006801:Humans; D007624:KB Cells; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D013094:Spermatozoa / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D013844:Thiazoles; C560953:benzo(d)thiazol-2-amine; D010984:Platinum; D010165:Palladium; D004247:DNA