ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon activity.
ortho-Carboranylphenoxy derivatives were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter gene assay. Among the compounds synthesized, compound 1d showed the most significant inhibition of hypoxia-induced HIF-1 transcriptional activity with the IC50 of 0.53μM. Furthermore, compound 1h was found to possess the most significant inhibition of heat shock protein (HSP) 60 chaperon activity among the reported inhibitors: the IC50 toward the porcine heart malate dehydrogenase (MDH) refolding assay was 0.35μM.
['Li|Guangzhe|G|', 'Azuma|Soyoko|S|', 'Sato|Shinichi|S|', 'Minegishi|Hidemitsu|H|', 'Nakamura|Hiroyuki|H|']
D000083:Acetanilides D000818:Animals D001897:Boronic Acids D018834:Chaperonin 60 D015195:Drug Design D006367:HeLa Cells D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D007700:Kinetics D008291:Malate Dehydrogenase D024101:Mitochondrial Proteins D058849:Protein Refolding D013329:Structure-Activity Relationship D013552:Swine
Inhibitor Heat shock protein (HSP) 60 Angiogenesis Carborane Hypoxia-inducible factor (HIF)-1α