Synthesis, structural characterization and biological studies of the triphenyltin(IV) complex with 2-thiobarbituric acid

The reaction between 2-thiobarbituric acid (H2TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph3Sn(O-HTBA)]}n (1) complex. Crystals of the hydrated 1 with formula {[Ph3Sn(O-HTBA)]·0.7(H2O)}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)3Sn(O-HTBA)·H2O] (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.

Graphical abstractThe new complex {[Ph3Sn(O-HTBA)]·0.7(H2O)}n (1) is prepared, characterized and screened among with complex [(n-Bu)3Sn(TBA)·H2O] (2) against human cancer cell lines: HeLa, OAW-42, MCF-7, MDA-MB-231, A549, Caki-1, MRC-5 and MTSV17.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Structural characterization of a polymeric triphenyltin(IV) complex with 2-thiobarbituric acid. ► High cytostatic activity of triphenyltin(IV) complex with 2-thiobarbituric acid complexes. ► Experimental and theoretical study of the peroxidation of linoleic acid by the enzyme lipoxygenase in the presence of the organotin(IV) complex with 2-thiobarbituric acid.