Platinum(II)-thiosemicarbazone drugs override the cell resistance due to glutathione; assessment of their activity against human adenocarcinoma cells

WOS: 000387785800010New platinum(II) compounds of the thiosemicarbazone 1-(1H-Benzimidazol-2-yl)ethan-1-one thiosemicarbazone (BzimetTSCH), [Pt(BzimetTSCH)Cl]center dot 2H(2)O (1) and [Pt(BzimetTSCH)(tpp)]Cl center dot H2O center dot MeCN (2) were synthesized. The complexes were characterized by FT-IR spectroscopy and H-1 NMR spectroscopy. The crystal structures of 1 and 2 were determined with single-crystal X-ray diffraction analysis. The coordination around platinum is square planar in both complexes. Compounds 1 and 2 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma breast (MCF-7) and cervix (HeLa) cells. The apoptotic pathway of cell death was confirmed by cell cycle arrest test. Since deactivation of cisplatin caused by glutathione (GSH) seems to be an important determinant of its cytotoxic effects, the reactions of 1 and 2 with GSH were investigated by UV-absorption spectroscopy. The genotoxicities on normal human fetal lung fibroblast cells (MRC-5) caused by 1 and 2 were evaluated by fluorescence microscopy. The absence of micronucleus in MRC-5 cells confirms the in vitro non toxic behavior of the compounds. Moreover, the in vivo genotoxicities of 1 and 2 were evaluated by the Allium cepa test. Due to negligible genototoxic effect and high antitumor activity which is similar to that of cisplatin, 2 could be a candidate for further study as potential drug since the mitotic index is unchanged. [GRAPHICS] .Josef and Esther Gani Foundation [81455]; State Scholarships Foundation of Greece (IKY) IKY-Siemens [22957]CNB and SKH would like to thank (i) the Unit of bioactivity testing of xenobiotics, the University of Ioannina, for providing access to the facilities, (ii) the Atherothrombosis Research Centre of the University of Ioannina for providing access to the flow cytometer, (iii) the Josef and Esther Gani Foundation for the financial support (project number 81455), and (iv) the State Scholarships Foundation of Greece (IKY) for the post doctoral research fellowship of excellence program IKY-Siemens (project number 22957)