Recent advances in bacterial topoisomerase inhibitors

Bacterial topoisomerase inhibitors continue to be actively developed as clinical antibacterial agents, largely owing to the success of the currently marketed inhibitors, the quinolones, and the increasing resistance to these agents. New quinolone analogs such as isothiazoloquinolones and quinazoline...

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Bibliographic Details
Published in:Current opinion in pharmacology 2008-10, Vol.8 (5), p.574-581
Main Authors: Bradbury, Barton J, Pucci, Michael J
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Bacteria
Bacteria - drug effects
Bacteria - enzymology
Indazoles - pharmacology
Internal Medicine
Medical Education
Pyrazoles - pharmacology
Quinolones - pharmacology
Thiazoles - pharmacology
Topoisomerase I Inhibitors
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
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Summary:Bacterial topoisomerase inhibitors continue to be actively developed as clinical antibacterial agents, largely owing to the success of the currently marketed inhibitors, the quinolones, and the increasing resistance to these agents. New quinolone analogs such as isothiazoloquinolones and quinazolinediones show some potential in overcoming this problem. Quinolones linked to other antibacterial agents such as rifamycins and oxazolidinones are designed to overcome both quinolone-specific resistance and resistance to the coupled agents. Novel inhibitors targeting non-quinolone-binding regions of topoisomerase continue to expand beyond the known coumarin class. The benzimidazoles and pyrazoles have shown promise but have been surpassed into the clinic by novel quinolines. Improved screening techniques and high-throughput methods offer new hope of further expanding the chemical space of topoisomerase inhibitors.
ISSN:1471-4892
1471-4973
DOI:10.1016/j.coph.2008.04.009