title: ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon activity.
abstract: 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.
authors.affiliation: Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
authors.forename: Guangzhe
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Life Science, Faculty of Science, Gakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Soyoko
authors.initials: S
authors.lastname: Azuma
authors.affiliation: Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.affiliation: Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan; Department of Life Science, Faculty of Science, Gakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Minegishi
authors.affiliation: Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan. Electronic address: hiro@res.titech.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001897:Boronic Acids / Q000737:chemistry / Q000494:pharmacology; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors*; D058849:Protein Refolding / Q000187:drug effects; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000083:Acetanilides; D001897:Boronic Acids; D018834:Chaperonin 60; C549649:GN 26361; C497442:HIF1A protein, human; C060293:HSPD1 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D024101:Mitochondrial Proteins; D008291:Malate Dehydrogenase
keywords: Angiogenesis; Carborane; Heat shock protein (HSP) 60; Hypoxia-inducible factor (HIF)-1α; Inhibitor