Synthesis of substituted aromatic heterocyclic sulfonyl hydrazone compounds and in vitro anti-hepatoma activity: preliminary results

OBJECTIVE: Hydrazone compounds and their derivatives are a kind of special Schiff bases. The multiple hydrazone compounds and their derivatives have a variety of biological activities. This study aims to report the synthesis of diverse hydrazone derivatives and to explore the potent antitumor activities. MATERIALS AND METHODS: A series of aromatic heterocyclic sulfonyl hydrazones W1-W15 synthesized from hydrazine or acylhydrazine and aldehydes or ketones were estimated for their in vitro antitumor activities against human cancers. Through the spectral (FT-IR, H-1-NMR, MS) methods, the structure of the compounds was determined. Using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method, the effects of different concentrations of compounds on growth inhibition and viability of HepG-2 cells were detected. RESULTS: Compound W9 exhibited anti-proliferation activity with IC50 values of 63.91 mu mol/L in HepG-2 cell line. In addition, mechanism studies indicated that compound W9 could distinctly prohibit the propagation of HepG-2 cells by arresting the cell cycle at G(2)/M and inducing apoptosis. Furthermore, we investigated the effectiveness of drug combination treatment with W-9 and cis-platinum (cis-DDP) or 5-fluorouracil (5-FU) on HepG-2 cell line. CONCLUSIONS: Our results indicated that W9 with synergic treatment of 5-FU or cis-DDP shows better inhibitory cell growth. The combination of the two drugs blocks HepG-2 cells in the G(2)/M phase. The inhibitory effect of W9 on cell apoptosis was decreased with the increase of drug concentration.