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 journalArticle

57 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 languageEnglish
Pages (from-to)7061-7066
Number of pages6
JournalTetrahedron
Volume60
Issue number33
DOIs
Publication statusPublished - 2004 Aug 9

Fingerprint

Bioactivity
Apoptosis Regulatory Proteins
Enantiomers
Macrophages
Tetradecanoylphorbol Acetate
Purification
Monocytes
Acetates
Transcription Factors
dehydroxymethylepoxyquinomicin
Cytokines
Anti-Bacterial Agents

Keywords

  • Apoptosis
  • DHMEQ
  • Inflammation
  • NF-κB
  • Nuclear transport
  • Optical resolution

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor. / Suzuki, Yoshikazu; Sugiyama, Chie; Ohno, Osamu; Umezawa, Kazuo.

In: Tetrahedron, Vol. 60, No. 33, 09.08.2004, p. 7061-7066.

Research output: Contribution to journalArticle

Suzuki, Yoshikazu ; Sugiyama, Chie ; Ohno, Osamu ; Umezawa, Kazuo. / Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor. In: Tetrahedron. 2004 ; Vol. 60, No. 33. pp. 7061-7066.
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