Studies on Macrolide Antibiotics I. Synthesis and Antibacterial Activity of Erythromycin A 9-O-Substituted Oxime Ether Derivatives against Mycobacterium avium Complex.

• NISHIMOTO Akemi

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• NARITA Ken

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• OHMOTO Shinobu

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• TAKAHASHI Yoshie

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• YOSHIZUMI Satoshi

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• YOSHIDA Toshihiko

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• KADO Noriyuki

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• OKEZAKI Eichi

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

• KATO Hideo

  Research and Development Headquaters, Hokuriku Seiyaku Co., Ltd.

抄録

A series of erythromycin A 9-O-substituted oxime ether derivatives have been synthesized and evaluated for antibacterial activity against Mycobacterium avium complex (MAC) and Staphylococcus aureus. These compounds possessed stronger in vitro activity against MAC including macrolide-resistant strains than clarithromycin (2), although in vitro antibacterial activities of these compounds were less than that of 2 against Staphylococcus aureus. Our studies found that several factors contribute to the antibacterial activity against MAC. The length and spatial orientation of the substituent at 9-position were found to significantly influenced the anti-MAC activity, especially against macrolide-resistant strains. Of all the compounds prepared, erythromycin A 9-[O-(4-phenylbutyl)oxime] (12q) and erythromycin A 9-[O-(3-phenoxypropyl)oxime] (12t) possessed 16 times stronger antibacterial activity than 2 against clarithromycin-resistant strains. Surprisingly, the minimum inhibitory concentrations (MICs) of 12q and 12t against the resistant strains were almost same as those against the susceptible strains. These results suggest that the erythromycin A 9-O-substituted oxime ether derivatives would be promising macrolide antibiotics.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 49 (9), 1120-1127, 2001

  公益社団法人 日本薬学会

キーワード

• macrolide
• antibiotic
• antibacterial activity
• Mycobacterium avium complex
• erythromycin A 9-O-substituted oxime ether

詳細情報

• CRID: 1390282679141233408
• NII論文ID: 110003616060
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.49.1120
• COI: 1:CAS:528:DC%2BD3MXmsFyktr4%3D
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 5892724
• PubMed: 11558597
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5892724
• Web Site: http://www.jstage.jst.go.jp/article/cpb/49/9/49_9_1120/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2002024105
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可