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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Cyclothialidine and its congeners: a new class of DNA gyrase inhibitors.

Cyclothialidine is a new, potent DNA gyrase inhibitor isolated from Streptomyces filipinensis. However, it exhibits hardly any growth-inhibitory activity against intact bacterial cells. To explore its potential with regard to the development of a new type of antibacterial, a flexible synthetic route was worked out (i) to investigate the structural requirements for DNA gyrase inhibition and (ii) to search for congeners exerting antibacterial activity. The structure of cyclothialidine was confirmed by total synthesis. Marked DNA gyrase inhibitory activity was found for a number of analogs, a common feature of them being the bicyclic 12-membered lactone bearing one phenolic hydroxy group. Congeners of cyclothialidine were found to exhibit a moderate, but broad-spectrum, in vitro activity against Gram-positive bacteria. Therefore, the DNA gyrase inhibitory principle contained in cyclothialidine can be considered as the basis for a new class of antibacterial agents.[1]

References

  1. Cyclothialidine and its congeners: a new class of DNA gyrase inhibitors. Goetschi, E., Angehrn, P., Gmuender, H., Hebeisen, P., Link, H., Masciadri, R., Nielsen, J. Pharmacol. Ther. (1993) [Pubmed]
 
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