阿贝卡星衍生物4''-位结构变化对耐甲氧西林金黄色葡萄球菌和铜绿假单胞菌抗菌活性的影响。

Effect of varying the 4''-position of arbekacin derivatives on antibacterial activity against MRSA and Pseudomonas aeruginosa.

作者信息

Hiraiwa Yukiko, Minowa Nobuto, Usui Takayuki, Akiyama Yoshihisa, Maebashi Kazunori, Ikeda Daishiro

机构信息

Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Japan.

出版信息

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6369-72. doi: 10.1016/j.bmcl.2007.08.059. Epub 2007 Aug 28.

DOI:10.1016/j.bmcl.2007.08.059

PMID:17889537

Abstract

4''-Deoxy-4''-episubstituted arbekacin derivatives and 4''-epi-5-deoxy-5-episubstituted arbekacin derivatives were designed and synthesized. Arbekacin and 4''-epiarbekacin both displayed the same antibacterial activity against Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA)) and Pseudomonas aeruginosa. The 4''-epi-5-deoxy-5-episubstituted arbekacin derivatives showed potent antibacterial activity. Among them, the antibacterial activity of 5,4''-diepiarbekacin was superior to that of arbekacin or 5-episubstituted arbekacin against Gram-positive and Gram-negative bacteria. The 6'-N-methyl derivative of the 5,4''-diepiarbekacin was effective against P. aeruginosa expressing an aminoglycoside-modifying enzyme AAC(6')-Ib.

摘要

设计并合成了4''-脱氧-4''-表位取代阿贝卡星衍生物和4''-表位-5-脱氧-5-表位取代阿贝卡星衍生物。阿贝卡星和4''-表阿贝卡星对金黄色葡萄球菌（包括耐甲氧西林金黄色葡萄球菌（MRSA））和铜绿假单胞菌均表现出相同的抗菌活性。4''-表位-5-脱氧-5-表位取代阿贝卡星衍生物显示出强效抗菌活性。其中，5,4''-二表阿贝卡星对革兰氏阳性菌和革兰氏阴性菌的抗菌活性优于阿贝卡星或5-表位取代阿贝卡星。5,4''-二表阿贝卡星的6'-N-甲基衍生物对表达氨基糖苷修饰酶AAC(6')-Ib的铜绿假单胞菌有效。