Synthesis and anticancer activities of 1,4-phenylene-bis-N-acetyl- and N-phenylpyrazoline derivatives

Novel 1,4-phenylene-bis-N-acetyl- (3a-h) and bis-N-phenylpyrazoline derivatives (4a-h) were obtained by addition of hydrazine hydrate and phenylhydrazine to bis-chalcone derivatives (1a-h) in acetic acid and acetic acid/ethanol for 4 and 8 h in reflux conditions, respectively. The structures of the obtained bis-N-acetylpyrazoline and bis-N-phenylpyrazoline derivatives were characterized by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic methods and elemental analysis. Compounds 3a-h and 4a-h were investigated to evaluate their anticancer activities against C6 (rat brain tumor cells) and HeLa (human uterus carcinoma) in vitro using a dose-dependent assay from 5 to 100 mu M with 5-fluorouracil (5-FU) as standard anticancer drug. Compound 3a showed higher cell-selective activity compared with 5-FU against HeLa cells. Compounds 3a-h (except 3d) were shown to have better activities than 5-FU against both cells, particularly at high concentration. Compound 4c showed higher cell-selective activity compared with 5-FU against C6 cells. Compound 3a may be particularly promising as an anticancer drug against HeLa cells.