Synthesis and cytotoxicity of silicon and germanium containing pyridine oxime O-ethers

Abstract

Silicon and germanium containing pyridine aldoxime, ketoxime and amidoxime O-ethers have been prepared using phase transfer catalytic systems oxime / alkyl halide / solid KOH / 18-crown-6 / benzene and oxime / alkyl halide / solid K2CO3 or Cs2CO3 / 18-crown-6 / toluene. Cytotoxic activity of silicon and germanium containing pyridine oxime O-ethers was tested in vitro on two monolayer tumor cell lines: MG-22A (mouse hepatoma) and HT-1080 (human fibrosarcoma). O-[3-Triethylsilylpropyl]- and O-[3-(1-methyl-1-silacyclopentyl)propyl] oximes of pyridine aldehydes and ketones exhibit high cytotoxicity. Presence of methyl group in the pyridine ring considerably decreased activity of amidoxime O-ethers. Oxime ethers containing two elements are essentially inactive. For 2-acetylpyridine oxime ethers the activity increases in order of alkyl substituents: Et3GeCH 2CH2SiMe2CH2 < Et 3SiCH2CH2CH2 < (CH 2)4SiCH2CH2CH2. Cytotoxicity of ketoxime O-ethers is considerably lower in comparison with aldoxime O-ethers.