| Structural highlights
Function
GYRB_STAAU DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.[HAMAP-Rule:MF_01898]
Publication Abstract from PubMed
The emergence and spread of multidrug resistant bacteria are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the discovery of azaindole ureas as a novel class of bacterial gyrase B inhibitors and detail the story of their evolution from a de novo design hit based on structure-based drug design. These inhibitors show potent minimum inhibitory concentrations against fluoroquinolone resistant MRSA and other Gram-positive bacteria.
Discovery of Azaindole Ureas as a Novel Class of Bacterial Gyrase B Inhibitors.,Zhang J, Yang Q, Cross JB, Romero JA, Poutsiaka KM, Epie F, Bevan D, Wang B, Zhang Y, Chavan A, Zhang X, Moy T, Daniel A, Nguyen K, Chamberlain B, Carter N, Shotwell J, Silverman J, Metcalf CA 3rd, Ryan D, Lippa B, Dolle RE J Med Chem. 2015 Nov 12;58(21):8503-12. doi: 10.1021/acs.jmedchem.5b00961. Epub, 2015 Oct 22. PMID:26460684[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang J, Yang Q, Cross JB, Romero JA, Poutsiaka KM, Epie F, Bevan D, Wang B, Zhang Y, Chavan A, Zhang X, Moy T, Daniel A, Nguyen K, Chamberlain B, Carter N, Shotwell J, Silverman J, Metcalf CA 3rd, Ryan D, Lippa B, Dolle RE. Discovery of Azaindole Ureas as a Novel Class of Bacterial Gyrase B Inhibitors. J Med Chem. 2015 Nov 12;58(21):8503-12. doi: 10.1021/acs.jmedchem.5b00961. Epub, 2015 Oct 22. PMID:26460684 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00961
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