Diversity of complexes based on p-nitrobenzoylhydrazide, benzoylformic acid and diorganotin halides or oxides self-assemble: Cytotoxicity, the induction of apoptosis in cancer cells and DNA-binding properties

Abstract

Eight organotin(IV) complexes (C1-C8) have been synthesized and characterized by elemental analysis, fourier transform infrared spectroscopy (FT-IR), multinuclear nuclear magnetic resonance (¹H, ¹³C and ¹¹⁹Sn NMR), high resolution mass spectroscopy (HRMS) and single crystal X-ray structural analysis. Crystallographic data show that C1 was a tetranuclear 16-membered macrocycle complex, C2-C4 and C7 were centrosymmetric dimer distannoxane and there was a Sn₂O₂ four-membered ring in the middle of the molecule, respectively, C5 and C6 are monoorganotin complexes due to the dehydroalkylation effect during the reaction, while C8 forms a one-dimensional chain structure. The cytotoxicity of all complexes were tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays against three human tumor cell lines NCI-H460, MCF-7 and HepG2. The dibutyltin complex C2 has been shown to be more potent antitumor agents than other complexes and carboplatin. Cell apoptosis study of C2 with the high activity on HepG2 and MCF-7 cancer cell lines was investigated by flow cytometry, it was shown that the antitumor activity of C2 was related to apoptosis, but it has different cell cycle arrest characteristics from platinum compounds, and the proliferation was inhibited by blocking cells in S phase. The DNA binding activity of the C2 was studied by UV-visible absorption spectrometry, fluorescence competitive, viscosity measurements and gel electrophoresis, results shown C2 can be well embedded in the double helix of DNA and cleave DNA.

Keywords: Apoptosis; Crystal structure; Organotin complex; Self-assemble; Synthesis.