Diorganotin(IV) complexes based on tridentate ONO ligands as potential anticancer agents

Eight new diorganotin(IV) complexes (1a-2d), namely {[X-C6H4(O)C=N-N=C(Me)COO]R2Sn(CH3OH)}(n) (1a, 2a), {[X-C6H4(O)C=N-N=C(Me)COO]R2Sn(CH3OH)}(2) (1b, 1c, 1d, 2b), and {[X-C6H4(O)C=N-N=C(Me)COO]R2Sn}(2) (2c, 2d) (X = H-, p-Me-, p-OH-, p-NO2-; R = o-Cl-C6H4CH2- or o-Me-C6H4CH2-), have been synthesized by microwave one-pot reaction with arylformylhydrazine, pyruvic acid, and the corresponding R2SnCl2. All the complexes have been characterized by FT-IR (Fourier transform infrared spectroscopy), multinuclear NMR (H-1, C-13, and Sn-119 nuclear magnetic resonance spectroscopies), HRMS (high-resolution mass spectroscopy) and single-crystal X-ray structural analysis. The antiproliferative activity of all complexes was tested against the cancer cell lines NCI-H460, MCF-7 and HepG2. The diorganotin complex 1c has been shown to be more potent antitumor agents against HepG2 than other complexes and cisplatin. Flow cytometry analysis observation demonstrated that complex 1c mediated cell apoptosis of HepG2 cells and arrested cell cycle in the S phase. The single cell gel electrophoreses assay results show that the 1c induce DNA damage. The DNA binding activities of the 1c were studied by UV-visible absorption spectrometry, fluorescence competitive, circular dichroism measurements, and molecular docking, results shown 1c can be well embedded in the groove and cleave DNA.

Automated summary

In this study, eight new diorganotin(IV) complexes were synthesized and their structures were characterized. The antiproliferative activity of the complexes was tested, and complex 1c showed stronger antitumor activity, inducing cell apoptosis and DNA damage.