Design, synthesis and biological evaluation of cinnamic acyl shikonin derivatives.
Inducing apoptosis is an important and promising therapeutic approach to overcome cancer. Here, we described a series of novel synthesized compounds, cinnamic acyl shikonin derivatives (1b-19b), which were synthesized starting from shikonin and cinnamic acids, which exhibit anticancer activity via inducing apoptosis in vitro. Our flow cytometry results showed that compound 8b((E)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent -3-enyl-3-(3-(trifluoromethyl) phenyl)acrylate) (IC(50) = 0.69, 0.65, 1.62 μM for human SW872-s, A875 and A549 cell lines, respectively) exhibited conspicuous anticancer activities and has low cell toxicity in vitro. Therefore, we considered that compound 8b is potentially to be a candidate of anticancer agent. The proliferation inhibitory effect of compound 8b was associated with its apoptosis-inducing effect by activating caspase-3, caspase-7, caspase-9, and PARP. When the level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, and cleaved PARP are rise, apoptosis of cancer cells will be induced.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
Hong-Yan
HY
Lin
Wei
W
Chen
Jing
J
Shi
Wen-Yao
WY
Kong
Jin-Liang
JL
Qi
Xiao-Ming
XM
Wang
Yong-Hua
YH
Yang
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
C586338:1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl-3-(3-(trifluoromethyl)phenyl)acrylate; D000970:Antineoplastic Agents; D002934:Cinnamates; D009285:Naphthoquinones; C016101:shikonin; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9