Synthesis and biological evaluation of hybrids from farnesylthiosalicylic acid and hydroxylcinnamic acid with dual inhibitory activities of Ras-related signaling and phosphorylated NF-κB.
A series of hybrids (5a–r) of farnesylthiosalicylic acid (FTS) and hydroxylcinnamic acid were designed and synthesized. Most of the hybrids displayed potent antiproliferative activity against seven cancer cell lines in vitro, superior to FTS as well as sorafenib. The most potent compound 5f selectively inhibited cancer cells but not non-tumor liver cell proliferation in vitro, and significantly induced SMMC-7721 cell apoptosis. Interestingly, 5f could simultaneously inhibit not only Ras-related signaling but also phosphorylated NF-κB, which may synergetically contribute to the cell growth inhibition and apoptosis induction. Moreover, 5f showed low acute toxicity to mice and significantly inhibited the hepatoma tumor growth.
School of Pharmacy, Nantong University, Nantong, 226001, PR China.
Yong
Y
Ling
Zhiqiang
Z
Wang
Xuemin
X
Wang
Ying
Y
Zhao
Wei
W
Zhang
Xinyang
X
Wang
Li
L
Chen
Zhangjian
Z
Huang
Yihua
Y
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003373:Coumaric Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D005204:Farnesol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D020128:Inhibitory Concentration 50; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012459:Salicylates / Q000138:chemical synthesis* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D003373:Coumaric Acids; D016328:NF-kappa B; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D018631:ras Proteins