title: Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents.
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.
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, and The Kitasato Institute 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sugawara
authors.forename: Akito
authors.initials: A
authors.lastname: Sueki
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nagai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shima
authors.forename: Kiyoko S
authors.initials: KS
authors.lastname: Akagawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: C560918:(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A; D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D018942:Macrolides; D004917:Erythromycin