Socha Aaron M, LaPlante Kerry L, Rowley David C
Department of Biomedical, University of Rhode Island, 53 Fogarty Hall Kingston, RI 02881, USA.
Bioorg Med Chem. 2006 Dec 15;14(24):8446-54. doi: 10.1016/j.bmc.2006.08.038. Epub 2006 Sep 18.
The escalation of antibiotic resistance among Gram-positive pathogens presents increasing treatment challenges and requires the development of innovative therapeutic agents. Here, we present the antimicrobial properties of structurally unusual bisanthraquinone metabolites produced by a marine streptomycete and four semi-synthetic derivatives. Biological activities were measured against clinically derived isolates of vancomycin-resistant Enterococcus faecium (VRE), and methicillin-susceptible, methicillin-resistant, and tetracycline-resistant Staphylococcus aureus (MSSA, MRSA, and TRSA, respectively). The most potent antibiotic displayed MIC(50) values of 0.11, 0.23, and 0.90microM against a panel (n=25 each) of clinical MSSA, MRSA, and VRE, respectively, and was determined to be bactericidal by time-kill analysis.
革兰氏阳性病原体中抗生素耐药性的不断升级给治疗带来了越来越多的挑战，需要开发创新的治疗药物。在此，我们展示了一种海洋链霉菌产生的结构不寻常的双蒽醌代谢产物及其四种半合成衍生物的抗菌特性。针对临床分离的耐万古霉素粪肠球菌（VRE）以及甲氧西林敏感、甲氧西林耐药和四环素耐药金黄色葡萄球菌（分别为MSSA、MRSA和TRSA）测定了生物活性。最有效的抗生素对一组（每组n = 25）临床MSSA、MRSA和VRE的MIC(50)值分别为0.11、0.23和0.90微摩尔，并且通过时间杀菌分析确定其具有杀菌作用。
