| Literature DB >> 21332115 |
Rohan A Davis1, Andreas Hofmann, Asiah Osman, Rebecca A Hall, Fritz A Mühlschlegel, Daniela Vullo, Alessio Innocenti, Claudiu T Supuran, Sally-Ann Poulsen.
Abstract
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 β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as α-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal β-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 β over α 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.Entities:
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Year: 2011 PMID： 21332115 DOI： 10.1021/jm1013242
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446