|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
6
|
|
pubmed:dateCreated |
2011-3-17
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
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 ?-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, and Cryptococcus neoformans as well as ?-family human CA I and CA II for comparison. Many of the NPs selectively inhibited the mycobacterial and fungal ?-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 ? over ? 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.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
1520-4804
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
24
|
|
pubmed:volume |
54
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1682-92
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:21332115-Anti-Bacterial Agents,
pubmed-meshheading:21332115-Antifungal Agents,
pubmed-meshheading:21332115-Biological Agents,
pubmed-meshheading:21332115-Candida albicans,
pubmed-meshheading:21332115-Carbonic Anhydrase I,
pubmed-meshheading:21332115-Carbonic Anhydrase II,
pubmed-meshheading:21332115-Carbonic Anhydrase Inhibitors,
pubmed-meshheading:21332115-Carbonic Anhydrases,
pubmed-meshheading:21332115-Catalytic Domain,
pubmed-meshheading:21332115-Cryptococcus neoformans,
pubmed-meshheading:21332115-Crystallography, X-Ray,
pubmed-meshheading:21332115-Humans,
pubmed-meshheading:21332115-Hydrogen Bonding,
pubmed-meshheading:21332115-Isoenzymes,
pubmed-meshheading:21332115-Models, Molecular,
pubmed-meshheading:21332115-Molecular Structure,
pubmed-meshheading:21332115-Mycobacterium tuberculosis,
pubmed-meshheading:21332115-Phenols,
pubmed-meshheading:21332115-Protein Binding,
pubmed-meshheading:21332115-Small Molecule Libraries
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases.
|
|
pubmed:affiliation |
Eskitis Institute, Griffith University, Nathan, Queensland 4111, Australia.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
