Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents

Akihiro Sugawara; Akito Sueki; Tomoyasu Hirose; Kenichiro Nagai; Hiroaki Gouda; Shuichi Hirono; Hideaki Shima; Kiyoko S. Akagawa; Satoshi Õmura; Toshiaki Sunazuka

doi:10.1016/j.bmcl.2011.04.004

Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents

Akihiro Sugawara, Akito Sueki, Tomoyasu Hirose, Kenichiro Nagai, Hiroaki Gouda, Shuichi Hirono, Hideaki Shima, Kiyoko S. Akagawa, Satoshi Õmura, Toshiaki Sunazuka

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3373-3376
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2011.04.004
Publication status	Published - 2011 Jun 1
Externally published	Yes

Keywords

(8R,9S)-8,9-Dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900)
14-Membered non-antibiotic macrolide
Anti-inflammatory agent
Diffuse panbronchiolitis
Immunomodulatory agent

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2011.04.004

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Sugawara, A., Sueki, A., Hirose, T., Nagai, K., Gouda, H., Hirono, S., Shima, H., Akagawa, K. S., Õmura, S., & Sunazuka, T. (2011). Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents. Bioorganic and Medicinal Chemistry Letters, 21(11), 3373-3376. https://doi.org/10.1016/j.bmcl.2011.04.004

Sugawara, A, Sueki, A, Hirose, T, Nagai, K, Gouda, H, Hirono, S, Shima, H, Akagawa, KS, Õmura, S & Sunazuka, T 2011, 'Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 11, pp. 3373-3376. https://doi.org/10.1016/j.bmcl.2011.04.004

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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.",

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AU - Hirono, Shuichi

AU - Shima, Hideaki

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Novel 12-membered non-antibiotic macrolides from erythromycin A; EM900 series as novel leads for anti-inflammatory and/or immunomodulatory agents

Abstract

Keywords

ASJC Scopus subject areas

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