Ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon activity

Guangzhe Li; Soyoko Azuma; Shinichi Sato; Hidemitsu Minegishi; Hiroyuki Nakamura

doi:10.1016/j.bmcl.2015.04.088

Ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon activity

Guangzhe Li, Soyoko Azuma, Shinichi Sato, Hidemitsu Minegishi, Hiroyuki Nakamura

PHA - Molecular Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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 0.53 μM. 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 0.35 μM.

Original language	English
Pages (from-to)	2624-2628
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2015.04.088
Publication status	Published - 2015 May 30

Keywords

Angiogenesis
Carborane
Heat shock protein (HSP) 60
Hypoxia-inducible factor (HIF)-1α
Inhibitor

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon activity. / Li, Guangzhe; Azuma, Soyoko; Sato, Shinichi; Minegishi, Hidemitsu; Nakamura, Hiroyuki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 13, 30.05.2015, p. 2624-2628.

Research output: Contribution to journal › Article › peer-review

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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 0.53 μM. 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 0.35 μM.",

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AU - Sato, Shinichi

AU - Minegishi, Hidemitsu

AU - Nakamura, Hiroyuki

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