Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands

Reactions of GaCl3 with pyrazole-containing ligands of the pyrazole-imine-phenol (HL1–HL3) or pyrazole-amine-phenol (HL4–HL6) types led to the synthesis of well-defined [GaL2]+ homoleptic complexes (1–6). Complexes 1–6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1–3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4–6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1–3 have a greater stability in solution compared to 4–6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1–6 and of the respective ligands (HL1–HL6) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL1 and HL6. The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways.

Cationic homoleptic Ga(III) complexes stabilized with two different families of pyrazole-containing ligands were successfully synthesized and characterized. The evaluation of their cytotoxic activity against MCF-7 and PC-3 human cancer cell lines has shown that the compounds with chloride substituents in the phenolate rings display the highest cytotoxicity and induce cell death mainly through an apoptotic pathway.Figure optionsDownload as PowerPoint slide