Bera Smritilekha, Zhanel George G, Schweizer Frank
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
J Med Chem. 2008 Oct 9;51(19):6160-4. doi: 10.1021/jm800345u. Epub 2008 Sep 9.
Aminoglycoside antibiotics and cationic detergents constitute two classes of clinically important drugs and antiseptics. Their bacteriological and clinical efficacy, however, has decreased recently due to antibiotic resistance. We have synthesized aminoglycoside-lipid conjugates in which the aminoglycoside neomycin forms the cationic headgroup of a polycationic detergent. Our results show that neomycin-C16 and neomycin-C20 conjugates exhibit strong Gram-positive activity but reduced Gram-negative activity. The MIC of neomycin-C16 (C20) conjugates against methicillin-resistant Staphylococcus aureus (MRSA) is comparable to clinically used antiseptics.
氨基糖苷类抗生素和阳离子去污剂是两类临床上重要的药物和防腐剂。然而，由于抗生素耐药性，它们的细菌学和临床疗效最近有所下降。我们合成了氨基糖苷-脂质缀合物，其中氨基糖苷新霉素形成了聚阳离子去污剂的阳离子头部基团。我们的结果表明，新霉素-C16和新霉素-C20缀合物表现出较强的革兰氏阳性菌活性，但革兰氏阴性菌活性降低。新霉素-C16（C20）缀合物对耐甲氧西林金黄色葡萄球菌（MRSA）的最低抑菌浓度与临床使用的防腐剂相当。
