Synthesis and biological evaluation of furoxan-based nitric oxide-releasing derivatives of glycyrrhetinic acid as anti-hepatocellular carcinoma agents.

Abstract

A series of novel furoxan-based nitric oxide (NO)-releasing derivatives of glycyrrhetinic acid (GA) were designed, synthesized, and evaluated for their in vitro cytotoxicity against human hepatocellular carcinoma (HCC) and non-tumor liver cells. Five furoxan/GA hybrids, 7b-d, 7f, and 7g, displayed potent cytotoxicity against HCC cells (IC(50): 0.25-1.10 μM against BEL-7402 cells and 1.32-6.78 μM against HepG2 cells), but had a little effect on the growth of LO2 cells, indicating that these compounds had selective cytotoxicity against HCC cells. Furthermore, these compounds produced high concentrations of NO in HCC cells, but low in LO2 cells and treatment with hemoglobin partially reduced the cytotoxicity of the hybrid in HCC cells. Apparently, the high concentrations of NO produced by NO donor moieties and the bioactivity of GA synergistically contribute to the cytotoxicity, but the NO is a major player against HCC cells in vitro. Potentially, our findings may aid in the design of new chemotherapeutic reagents for the intervention of human HCC at clinic.

• Authors: Yisheng Lai, Lihong Shen, Zhenzhen Zhang, Wenqing Liu, Yihua Zhang, Hui Ji, Jide Tian
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 22 Pg. 6416-20 (Nov 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20932754 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• 1,2,5-oxadiazole 2-oxide
• Antineoplastic Agents
• Oxadiazoles
• Nitric Oxide
• Glycyrrhetinic Acid

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Glycyrrhetinic Acid (chemical synthesis, chemistry, pharmacology)
• Humans
• Liver Neoplasms (pathology)
• Nitric Oxide (metabolism)
• Oxadiazoles (chemistry)