Synthesis, characterization and in vitro biological evaluation of novel organotin(IV) compounds with derivatives of 2-(5-arylidene-2,4- dioxothiazolidin-3-yl)propanoic acid

Abstract

Two novel triphenyltin(IV) compounds, [Ph3SnL1] (L1 = 2-(5-(4-fluorobenzylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (1)) and [Ph3SnL2] (L2 = 2-(5-(5-methyl-2-furfurylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (2)) were synthesized and characterized by FT-IR, (1H and 13C) NMR spectroscopy,mass spectrometry, and elemental microanalysis. The in vitro anticancer activity of the synthesized organotin(IV)compounds was determined against four tumor cell lines: PC-3 (prostate), HT-29 (colon), MCF-7 (breast), andHepG2 (hepatic) using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystalviolet) assays. The IC50 values are found to be in the range from 0.11 to 0.50 μM. Compound 1 exhibits thehighest activity toward PC-3 cells (IC50 = 0.115 } 0.009 μM; CV assay). The tin and platinum uptake in PC-3cells showed a threefold lower uptake of tin in comparison to platinum (as cisplatin). Together with its higheractivity this indicates a much higher cell inhibition potential of the tin compounds (calculated to ca. 50 to 100times). Morphological analysis suggested that the compounds induce apoptosis in PC-3 cells, and flow cytometryanalysis revealed that 1 and 2 induce autophagy as well as NO (nitric oxide) production.