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

Access to Document

10.1016/j.bmcl.2015.04.088

Cite this

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

@article{3b6132bb450e49d5b533292fbc072388,

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 0.53 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.",

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

author = "Guangzhe Li and Soyoko Azuma and Shinichi Sato and Hidemitsu Minegishi and Hiroyuki Nakamura",

note = "Funding Information: This work was partially supported by a Grant-in-Aid for Scientific Research on Innovative Areas {\textquoteleft}Chemical Biology of Natural Products{\textquoteright} from The Ministry of Education, Culture, Sports, Science and Technology, Japan . Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",

year = "2015",

month = may,

day = "30",

doi = "10.1016/j.bmcl.2015.04.088",

language = "English",

volume = "25",

pages = "2624--2628",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "13",

}

TY - JOUR

T1 - Ortho-Carboranylphenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity and heat shock protein (HSP) 60 chaperon activity

AU - Li, Guangzhe

AU - Azuma, Soyoko

AU - Sato, Shinichi

AU - Minegishi, Hidemitsu

AU - Nakamura, Hiroyuki

N1 - Funding Information: This work was partially supported by a Grant-in-Aid for Scientific Research on Innovative Areas ‘Chemical Biology of Natural Products’ from The Ministry of Education, Culture, Sports, Science and Technology, Japan . Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/5/30

Y1 - 2015/5/30

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Carborane

KW - Heat shock protein (HSP) 60

KW - Hypoxia-inducible factor (HIF)-1α

KW - Inhibitor

UR - http://www.scopus.com/inward/record.url?scp=84930091269&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930091269&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2015.04.088

DO - 10.1016/j.bmcl.2015.04.088

M3 - Article

C2 - 25981686

AN - SCOPUS:84930091269

VL - 25

SP - 2624

EP - 2628

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 13

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this