Design, synthesis, and antihepatocellular carcinoma activity of nitric oxide releasing derivatives of oleanolic acid.
Novel furoxan-based nitric oxide (NO) releasing derivatives of oleanolic acid (OA) were synthesized for potential therapy of liver cancers. Six compounds produced high levels of NO in human hepatocellular carcinoma (HCC) cells and exhibited strong cytotoxicity selectively against HCC in vitro. Treatment with 8b or 16b significantly inhibited the growth of HCC tumors in vivo. These data provide a proof-in-principle that furoxan/OA hybrids may be used for therapeutic intervention of human liver cancers.
Chen
Li
L
Department of Phytochemistry, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China.
Zhang
Yihua
Y
Kong
Xiangwen
X
Lan
Edward
E
Huang
Zhangjian
Z
Peng
Sixun
S
Kaufman
Daniel L
DL
Tian
Jide
J
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D009828:Oleanolic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009569:Nitric Oxide; D009828:Oleanolic Acid