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Title
Japanese:Development of hypoxia-inducible factor (HIF)-1ﾎｱ inhibitors: Effect of ortho-carborane substituents on HIF transcriptional activity under hypoxia 
English:Development of hypoxia-inducible factor (HIF)-1ﾎｱ inhibitors: Effect of ortho-carborane substituents on HIF transcriptional activity under hypoxia 
Author
Japanese: Hiroyuki Nakamura, Yuka Yasui, Minako Maruyama, Hidemitsu Minegishi, Hyun Seung Ban, Shinichi Sato.  
English: Hiroyuki Nakamura, Yuka Yasui, Minako Maruyama, Hidemitsu Minegishi, Hyun Seung Ban, Shinichi Sato.  
Language English 
Journal/Book name
Japanese:Bioorganic & Medicinal Chemistry Letters 
English:Bioorganic & Medicinal Chemistry Letters 
Volume, Number, Page Vol. 23        pp. 806-810
Published date Dec. 8, 2012 
Publisher
Japanese: 
English: 
Conference name
Japanese: 
English: 
Conference site
Japanese: 
English: 
Official URL http://www.sciencedirect.com/science/article/pii/S0960894X12015338
 
DOI https://doi.org/10.1016/j.bmcl.2012.11.081
Abstract A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI50) using the MTT assay. Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC50: 1.9 ± 0.4 and 1.4 ± 0.2 μM, respectively). Both compounds suppressed HIF-1α accumulation in a concentration-dependent manner. The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC50: 6.80 ± 0.25 μM) and this inhibition activity was higher than that of ETB (IC50: 10.9 ± 0.63 μM).

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