基于吲哚的双脒类抗生素具有强大而广谱的抗菌活性：MBX 1066 和 MBX 1090 新型类似物的合成及 SAR 研究。
Potent and broad-spectrum antibacterial activity of indole-based bisamidine antibiotics: synthesis and SAR of novel analogs of MBX 1066 and MBX 1090.
机构信息
Microbiotix, Inc., 1 Innovation Drive, Worcester, MA 01604, USA.
出版信息
Bioorg Med Chem. 2013 Dec 15;21(24):7790-806. doi: 10.1016/j.bmc.2013.10.014. Epub 2013 Oct 25.
Abstract
The prevalence of drug-resistant bacteria in the clinic has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We have previously described a set of bisamidine antibiotics that contains a core composed of two indoles and a central linker. The first compounds of the series, MBX 1066 and MBX 1090, have potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. We have conducted a systematic exploration of the amidine functionalities, the central linker, and substituents at the indole 3-position to determine the factors involved in potent antibacterial activity. Some of the newly synthesized compounds have even more potent and broad-spectrum activity than MBX 1066 and MBX 1090.
摘要
临床上耐药菌的流行促使人们齐心协力寻找新的抗生素类别，以规避当前的耐药模式。我们之前描述了一组双脒类抗生素，其核心由两个吲哚和一个中央连接子组成。该系列的第一批化合物 MBX 1066 和 MBX 1090 对多种革兰氏阳性和革兰氏阴性菌具有很强的抗菌活性。我们对脒基官能团、中央连接子以及吲哚 3 位的取代基进行了系统的研究，以确定与强抗菌活性相关的因素。一些新合成的化合物比 MBX 1066 和 MBX 1090 具有更强和更广谱的活性。
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