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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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