Antimicrobial lexitropsins containing amide, amidine, and alkene linking groups
Antimicrobial lexitropsins containing amide, amidine, and alkene linking groups
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DOI：
10.1021/jm070831g
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发表时间：
2007-11-29
影响因子：
7.3
通讯作者：
Waiah, Roger D.
中科院分区：
文献类型：
--
作者：
Anthony, Nahoum G.;Breerl, David;Waiah, Roger D.
本文报道了与偏端霉素和硫氮霉素有关的80个小沟结合剂的合成和性质。化合物的设计主要基于小沟结合剂和DNA之间的疏水相互作用引起的亲和力增加。引入疏水芳香族头基，包括喹啉基和苯甲酰基衍生物，以及烯烃作为连接体，产生了几种强活性的抗菌化合物，其对金黄色葡萄球菌（包括甲氧西林敏感和耐药菌株）的MIC在0.1-5 μ g mL（-1）的范围内，这与许多已建立的抗菌剂相当。抗真菌活性也被发现在20-50 μ g mL（-1）MIC范围内对尼日尔和白色念珠菌，再次与已建立的抗真菌药物。喹啉衍生物被发现可以保护小鼠免受S。金黄色葡萄球菌感染的一段时间长达6天后，单次腹腔注射剂量为40毫克kg（-1）。
The synthesis and properties of 80 short minor groove binders related to distamycin and the thiazotropsins are described. The design of the compounds was principally predicated upon increased affinity arising from hydrophobic interactions between minor groove binders and DNA. The introduction of hydrophobic aromatic head groups, including quinolyl and benzoyl derivatives, and of alkenes as linkers led to several strongly active antibacterial compounds with MIC for Staphylococcus aureus, both methicillin-sensitive and -resistant strains, in the range of 0.1-5 mu g mL(-1), which is comparable to many established antibacterial agents. Antifungal activity was also found in the range of 20-50 mu g mL(-1) MIC against Aspergillus niger and Candida albicans, again comparable with established antifungal drugs. A quinoline derivative was found to protect mice against S. aureus infection for a period of up to six days after a single intraperitoneal dose of 40 mg kg(-1).