Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis
Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis
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DOI：
10.1021/acs.jmedchem.5b01833
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发表时间：
2016-07-14
影响因子：
7.3
通讯作者：
Aube, Jeffrey
中科院分区：
文献类型：
--
作者：
Gold, Ben;Smith, Robert;Aube, Jeffrey
我们报道了两种新型头孢菌素系列，它们对测试的病原体中的结核分枝杆菌具有单独的杀菌作用，只有当结核分枝杆菌的复制被认为与宿主相似的条件所阻止时，它们才能杀死结核分枝杆菌，并且其杀菌活性不依赖于或增强克拉维酸，一种β -内酰胺酶抑制剂。这两类头孢菌素在头孢菌素环系统的C-2上有一个酯或一个恶二唑异异构体，在这类临床使用的药物中，这个位置几乎完全是羧酸。该系列的代表杀死巨噬细胞内的结核分枝杆菌，对巨噬细胞或其他哺乳动物细胞没有毒性。
We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a beta-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity tothe macrophages or other mammalian cells.