Citation: LI Shanhua, HUANG Zhining, MIAO Fangxiao, ZHENG Manyi, LIANG Han, WANG Baorui, QU Ning, QIAO Hong, WANG Haili, LI Funan. Synthesis and Anti-Hepatoma Activities of 1, 3-Substituted Indazole Derivatives as Hypoxia Induced Factor Inhibitors[J]. Chinese Journal of Applied Chemistry, ;2018, 35(4): 410-419. doi: 10.11944/j.issn.1000-0518.2018.04.170098 shu

Synthesis and Anti-Hepatoma Activities of 1, 3-Substituted Indazole Derivatives as Hypoxia Induced Factor Inhibitors

LI Shanhua ^a,, ,
HUANG Zhining ^b ,
MIAO Fangxiao ^a ,
ZHENG Manyi ^b ,
LIANG Han ^b ,
WANG Baorui ^b ,
QU Ning ^a ,
QIAO Hong ^a ,
WANG Haili ^b ,
LI Funan ^b

a.
Medical College, Xiamen University, Xiamen, Fujian 361102, China
b.
School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361102, China

Corresponding author: LI Shanhua, lish@xmu.edu.cn
Received Date: 31 March 2017
Revised Date: 20 June 2017
Accepted Date: 10 July 2017

Fund Project: XMU Training Program of Innovation and Enterpreneurship for Undergraduates 2016X0644the Natural Science Foundation of Fujian Province of China 2015Y0081XMU Training Program of Innovation and Enterpreneurship for Undergraduates 20720152005Supported by the Natural Science Foundation of Fujian Province of China(No.2015Y0081, No.2015J01350), XMU Training Program of Innovation and Enterpreneurship for Undergraduates(No.2016X0644, No.20720152005)the Natural Science Foundation of Fujian Province of China 2015J01350

Figures(5)

Hypoxia-inducible factor 1(HIF-1) is closely related to the growth, invasion and drug resistance of tumor cells and is highly expressed in tumor cells, so new HIF-1 inhibitors can be used as potential antitumor drugs. Nine 1, 3-substituted indazole derivatives were synthesized. The expression of HIF-1 and its target gene vascular endothelial growth factor(VEGF) were detected by Western Blot and Real time-PCR(polymerase chain reaction), and the anti-tumor activities of all the newly synthesized compounds were evaluated on the in vitro growth of HepG2 cell line taking 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1)(compound 7d) as positive control. We found that compound 7b significantly inhibited the expression of HIF-1 and its downstream target gene VEGF, and the anti-hepatoma biological activity in vitro of compound 7b was better than that of YC-1 with half maximal inhibitory concentration(IC₅₀) values of 10.37 μmol/L. The results show that 3-(5'-hydroxy methyl-2'-furan)-1-(1' -p-tolylsulfonyl) indazole targets the inhibition of HIF activity, but also has a good anti-hepatoma activity.
- indazole,
- hepG2 cells,
- hypoxia-inducible factor 1,
- anti-hepatoma activity
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