title: Synthesis, structural characterization and biological studies of the triphenyltin(IV) complex with 2-thiobarbituric acid.
abstract: The reaction between 2-thiobarbituric acid (H(2)TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph(3)Sn(O-HTBA)]}(n) (1) complex. Crystals of the hydrated 1 with formula {[Ph(3)Sn(O-HTBA)]·0.7(H(2)O)}(n) were growth from methanol/acetonitrile solution, of the white precipitation, filtered off, from the reaction. The crystal structure of complex 1 has been determined by X-ray diffraction at 120 K. Complex 1 is polymeric. The geometry around the tin(IV) ions is trigonal bi-pyramidal with coordination to three C atoms from phenyl groups and one O atom from a de-protonated HTBA ligand. Complex 1 and the already known [(n-Bu)(3)Sn(O-HTBA)·H(2)O] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (cervical), OAW-42 (ovarian), MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (renal) and additionally, the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line MTSV17 with a Trypan Blue assay. Moreover complex 1 was evaluated for its in vitro cell growth proliferation activity against leiomyosarcoma cells (LMS), MCF-7 and MRC-5 cells with a Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The type of cell death caused by complexes 1 and 2 was also evaluated by use of flow cytometry assay. The results showed that these compounds mediate a strong cytotoxic response to normal and cancer cell lines tested through apoptosis and induce cell cycle arrest in S phase of the cell cycle, suggesting DNA intercalation (direct or indirect) with the complexes. Finally, the influence of these complexes 1 and 2 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied.
authors.affiliation: Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: V I
authors.initials: VI
authors.lastname: Balas
authors.forename: I I
authors.initials: II
authors.lastname: Verginadis
authors.forename: G D
authors.initials: GD
authors.lastname: Geromichalos
authors.forename: N
authors.initials: N
authors.lastname: Kourkoumelis
authors.forename: L
authors.initials: L
authors.lastname: Male
authors.forename: M B
authors.initials: MB
authors.lastname: Hursthouse
authors.forename: K H
authors.initials: KH
authors.lastname: Repana
authors.forename: E
authors.initials: E
authors.lastname: Yiannaki
authors.forename: K
authors.initials: K
authors.lastname: Charalabopoulos
authors.forename: T
authors.initials: T
authors.lastname: Bakas
authors.forename: S K
authors.initials: SK
authors.lastname: Hadjikakou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019787:Linoleic Acid / Q000737:chemistry; D008084:Lipoxygenase / Q000737:chemistry; D061986:MCF-7 Cells; D009947:Organotin Compounds / Q000737:chemistry*; D017680:Potassium Compounds / Q000737:chemistry; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006878:Hydroxides; D007364:Intercalating Agents; D009947:Organotin Compounds; D017680:Potassium Compounds; D013858:Thiobarbiturates; C030665:triphenyltin; D019787:Linoleic Acid; D008084:Lipoxygenase; C029684:thiobarbituric acid; C029943:potassium hydroxide