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

D.-C. Wei, Y. Pan, H. Wang, W.-J. Xu, C. Chen, J.-H. Zheng, D. Cai

Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. jinhongzheng@sohu.com

---

• Pharmacology

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, 1H-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 μmol/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 G2/M and inducing apoptosis. Furthermore, we investigated the effectiveness of drug combination treatment with W9 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 G2/M phase. The inhibitory effect of W9 on cell apoptosis was decreased with the increase of drug concentration.

Free PDF Download