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

doi:10.11944/j.issn.1000-0518.2018.04.170098

Chinese Journal of Applied Chemistry ›› 2018, Vol. 35 ›› Issue (4): 410-419.DOI: 10.11944/j.issn.1000-0518.2018.04.170098

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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

^aMedical College
^bSchool of Pharmaceutical Sciences,Xiamen University,Xiamen,Fujian 361102,China

Received:2017-03-31 Accepted:2017-07-10 Published:2018-03-30 Online:2018-04-02
Contact: LI Shanhua
Supported by:
Supported 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)

Abstract

Abstract:

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.

Key words: indazole, hepG2 cells, hypoxia-inducible factor 1, anti-hepatoma activity

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.

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

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