Glycosylated diazeniumdiolate-based oleanolic acid derivatives: synthesis, in vitro and in vivo biological evaluation as anti-human hepatocellular carcinoma agents.

Abstract

A series of O(2)-glycosylated diazeniumdiolate-based derivatives of oleanolic acid (4-19) were synthesized and their anti-human hepatocellular carcinoma (HCC) activities were evaluated. Compound 6 selectively inhibited HCC, but not non-tumor liver cell proliferation. This inhibition was attributed to high levels of nitric oxide (NO) released in HCC cells. Importantly, 6 exhibited low acute toxicity (LD(50) = 173.3 mg kg(-1)) and potent inhibition of HCC tumor growth in mice (3 mg kg(-1) iv). Furthermore, 6 induced HCC cell apoptosis, which was accompanied by lower mitochondrial membrane potentials and Bcl2 expression, but with higher cytochrome C release, Bax, caspase 3 and 9 expression activities in HCC cells. Collectively, 6 may be a promising candidate drug for the intervention of HCC.

• Authors: Zhangjian Huang, Junjie Fu, Ling Liu, Yijun Sun, Yisheng Lai, Hui Ji, Edward E Knaus, Jide Tian, Yihua Zhang
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 10 Issue 19 Pg. 3882-91 (May 21 2012) ISSN: 1477-0539 [Electronic] England
• PMID: 22473516 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Azo Compounds
• diazeniumdiolate
• Oleanolic Acid

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, therapeutic use)
• Azo Compounds (chemistry)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Female
• Glycosylation
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Male
• Mice
• Molecular Structure
• Oleanolic Acid (analogs & derivatives, therapeutic use)
• Xenograft Model Antitumor Assays