2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III) complexes are highly cytotoxic to glioma cells

Abstract

2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone (H2AcpClPh) and paranitrophenylhydrazone (H2AcpNO2Ph) analogues, the corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and H2BzpNO2Ph) and their gallium(III) complexes were assayed for their cytotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. IC50 values against both glioma cells and against the MRC5 (human fetal lung fibroblast) lineage were obtained for the hydrazones, but not for their gallium(III) complexes, due to their low solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and T98 cells. The therapeutic indexes (TI ¼ IC50MRC5/IC50glioma) were 2-660 for T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could be good antitumor drug candidates to treat brain tumors.