Synthesis and biological evaluation of α-galactosylceramide analogues with heteroaromatic rings and varying positions of a phenyl group in the sphingosine backbone

Yongju Kim, Keunhee Oh, Heebum Song, Dong Sup Lee, Seung Bum Park

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We designed and synthesized seven α-GalCer analogues with a pyrazole moiety and varying positions of a phenyl group in the sphingosine backbone to polarize cytokine secretion. On the basis of in vitro and in vivo biological evaluations, we found that analogue 5 induced greater polarization toward Th2 and greater secretion of the immunomodulatory cytokine, IL-4, over secretion of pro-inflammatory cytokines, IFN-γ and IL-17. Treatment of a single dose of analogue 5 markedly ameliorated disease pathogenesis in an animal model of an inflammatory demyelinating disease of the central nervous system, compared to that of KRN7000 (1). Therefore, this new α-GalCer analogue 5 is a novel iNKT ligand that stimulates the selective secretion of anti-inflammatory cytokines and regulates autoimmune diseases by reducing Th1 and Th17 responses.

Original languageEnglish
Pages (from-to)7100-7109
Number of pages10
JournalJournal of Medicinal Chemistry
Volume56
Issue number17
DOIs
Publication statusPublished - 2013 Sep 12
Externally publishedYes

Fingerprint

Galactosylceramides
Sphingosine
Cytokines
Interleukin-17
Demyelinating Diseases
Interleukin-4
Autoimmune Diseases
Anti-Inflammatory Agents
Central Nervous System
Animal Models
Ligands

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis and biological evaluation of α-galactosylceramide analogues with heteroaromatic rings and varying positions of a phenyl group in the sphingosine backbone. / Kim, Yongju; Oh, Keunhee; Song, Heebum; Lee, Dong Sup; Park, Seung Bum.

In: Journal of Medicinal Chemistry, Vol. 56, No. 17, 12.09.2013, p. 7100-7109.

Research output: Contribution to journalArticle

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