期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 54, 期 6, 页码 1682-1692出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm1013242
关键词
-
资金
- Australian Research Council [DP0877554]
- European Union
- Australian Synchrotron
- Medical Research Council [G0601049] Funding Source: researchfish
- MRC [G0601049] Funding Source: UKRI
In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen beta-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as alpha-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal beta-CAs, with the two best performing compounds displaying submicromolar inhibition with a preference for fungal over human CA inhibition of more than 2 orders of magnitude. These compounds provide the first example of non-sulfonamide inhibitors that display beta over alpha CA enzyme selectivity. Structural characterization of the library compounds in complex with human CA II revealed a novel binding mode whereby a methyl ester interacts via a water molecule with the active site zinc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据