Novel 12-membered Non-Antibiotic Macrolides From Erythromycin A; EM900 Series as Novel Leads for Anti-Inflammatory and/or Immunomodulatory Agents

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3373-6. doi: 10.1016/j.bmcl.2011.04.004. Epub 2011 Apr 7.

Abstract

Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule shows improved acid stability, does not exhibit any anti-bacterial activity and has relatively low cytotoxicity against THP-1 cells. In addition, one of its analogues, (8R,9S)-4″,13-O-diacetyl-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM911), was found to be twice as effective as EM900.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Drug Design*
  • Erythromycin / analogs & derivatives*
  • Erythromycin / chemical synthesis
  • Erythromycin / chemistry*
  • Erythromycin / pharmacology
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Immunomodulation / drug effects*
  • Macrolides / chemical synthesis
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure

Substances

  • (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A
  • Anti-Inflammatory Agents
  • Immunologic Factors
  • Macrolides
  • Erythromycin