Synthesis, Structure and Cytotoxic Properties of Copper(II) Complexes of 2-Iminocoumarins Bearing a 1,3,5-Triazine or Benzoxazole/Benzothiazole Moiety.

A series of copper(II) complexes of 2-imino-2-chromen-3-yl-1,3,5-triazines , 3-(benzoxazol-2-yl)-2-chromen-2-imines , and 3-(benzothiazol-2-yl)-2-chromen-2-imines were obtained by reacting of appropriate 2-iminocoumarin ligands , , and with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (, , , and ). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes , , and with significant inhibitory properties toward tested tumor cell lines with IC values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands , , and , the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2-chromen-3-yl-1,3,5-triazines the most potent compound contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7' of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2-chromen-2-imines and 3-(benzothiazol-2-yl)-2-chromen-2-imines the most active was benzoxazole-2-iminocoumarin that also possessed a diethylamino group at position 7' of the 2-iminocoumarin moiety. Moreover, compound was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines.