title: 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.affiliation: Center of Drug Discovery, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Huang
authors.forename: Junjie
authors.initials: J
authors.lastname: Fu
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Sun
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Lai
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Edward E
authors.initials: EE
authors.lastname: Knaus
authors.forename: Jide
authors.initials: J
authors.lastname: Tian
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001391:Azo Compounds / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006031:Glycosylation; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001391:Azo Compounds; C452539:diazeniumdiolate; D009828:Oleanolic Acid