Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor

Yoshikazu Suzuki; Chie Sugiyama; Osamu Ohno; Kazuo Umezawa

doi:10.1016/j.tet.2004.01.103

Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor

Yoshikazu Suzuki, Chie Sugiyama, Osamu Ohno, Kazuo Umezawa

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

65 Citations (Scopus)

Abstract

NF-κB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-κB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-κB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells.

Original language	English
Pages (from-to)	7061-7066
Number of pages	6
Journal	Tetrahedron
Volume	60
Issue number	33
DOIs	https://doi.org/10.1016/j.tet.2004.01.103
Publication status	Published - 2004 Aug 9
Externally published	Yes

Keywords

Apoptosis
DHMEQ
Inflammation
NF-κB
Nuclear transport
Optical resolution

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2004.01.103

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title = "Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor",

abstract = "NF-κB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-κB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-κB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells.",

keywords = "Apoptosis, DHMEQ, Inflammation, NF-κB, Nuclear transport, Optical resolution",

author = "Yoshikazu Suzuki and Chie Sugiyama and Osamu Ohno and Kazuo Umezawa",

note = "Funding Information: This work was financially supported in part by grants from the Grants-in-Aid for Scientific Research on Priority Areas (A) of the Ministry of Education, Science, Culture, and Sports of Japan, and the Keio University Special Grants-in-Aid for Innovative Collaborative Research Projects.",

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doi = "10.1016/j.tet.2004.01.103",

language = "English",

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AU - Suzuki, Yoshikazu

AU - Sugiyama, Chie

AU - Ohno, Osamu

AU - Umezawa, Kazuo

N1 - Funding Information: This work was financially supported in part by grants from the Grants-in-Aid for Scientific Research on Priority Areas (A) of the Ministry of Education, Science, Culture, and Sports of Japan, and the Keio University Special Grants-in-Aid for Innovative Collaborative Research Projects.

PY - 2004/8/9

Y1 - 2004/8/9

N2 - NF-κB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-κB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-κB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells.

AB - NF-κB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-κB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-κB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells.

KW - Apoptosis

KW - DHMEQ

KW - Inflammation

KW - NF-κB

KW - Nuclear transport

KW - Optical resolution

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DO - 10.1016/j.tet.2004.01.103

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JO - Tetrahedron

JF - Tetrahedron

IS - 33

ER -

Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor

Abstract

Keywords

ASJC Scopus subject areas

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