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

被引：44

作者：

Sugawara, Akihiro ^{[1
,2
]}

Sueki, Akito ^{[1
,2
]}

Hirose, Tomoyasu ^{[1
,2
]}

Nagai, Kenichiro ^{[1
,2
]}

Gouda, Hiroaki ^{[3
]}

Hirono, Shuichi ^{[3
]}

Shima, Hideaki ^{[1
,2
]}

Akagawa, Kiyoko S. ^{[1
,2
]}

Omura, Satoshi ^{[1
,2
]}

Sunazuka, Toshiaki ^{[1
,2
]}

机构：

[1] Kitasato Univ, Kitasato Inst Life Sci, Minato Ku, Tokyo 1088641, Japan

[2] Kitasato Inst, Minato Ku, Tokyo 1088641, Japan

[3] Kitasato Univ, Sch Pharm, Minato Ku, Tokyo 1088641, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 11期

关键词：

(8R,9S)-8,9-Dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900); Anti-inflammatory agent; Immunomodulatory agent; 14-Membered non-antibiotic macrolide; Diffuse panbronchiolitis; MOTOR-STIMULATING ACTIVITY; N-SUBSTITUTED DERIVATIVES; MACROPHAGE DIFFERENTIATION; 8,9-ANHYDROERYTHROMYCIN-A 6,9-HEMIACETAL; MOTILIDES; MONOCYTE;

D O I：

10.1016/j.bmcl.2011.04.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3373 / 3376

页数：4

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