Dimeric diorganotin(iv) complexes with arylhydrazones of β-diketones: synthesis, structures, cytotoxicity and apoptosis properties

Abstract

Ten new dimeric diorganotin(IV) complexes of the type [R₂SnL]₂ (R = Me, Et, Bu, Ph or Oct, and H₂L = arylhydrazones of β-diketone) have been obtained by the reaction of the corresponding arylhydrazone of β-diketone with diorganotin(IV) dichloride under alkaline conditions. All the complexes were characterized by elemental analysis, IR and NMR (¹H, ¹³C, ¹¹⁹Sn) spectroscopies. Complexes 4 and 6 were also characterized by X-ray crystallography diffraction analysis, which revealed that the dimeric complexes have similar structures containing diorganotin(IV) skeletons formed by two weak but significant intermolecular Sn–O bonds. They were screened against the human tumor cell lines Hela, KB and HepG2. Complex 6 exhibited the highest in vitro cytotoxicity. The apoptosis induced by complexes 5, 6 and 9 was quantified using a flow cytometric assay. All the three organotin(IV) compounds induced apoptosis much more effectively than cisplatin, and the order of apoptosis induction is 6 > 5 > 9 > cisplatin. The results indicate that the apoptosis induction of the compounds correlates with the cytotoxicity. Moreover, quantification data of apoptosis in KB cells suggests that the mechanism of cell death might occur mainly by means of early apoptosis at more than 0.25 μM concentration of the complexes, which is beneficial for an optimal antitumor agent.