Abstract
The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-positive antibacterial activity and a low resistance frequency.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / antagonists & inhibitors
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Adenosine Triphosphatases / chemistry
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Anti-Infective Agents / pharmacology*
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Chemistry, Pharmaceutical / methods*
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DNA Topoisomerase IV / antagonists & inhibitors*
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Drug Design
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Enterococcus faecalis / metabolism
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Escherichia coli / metabolism
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Gram-Positive Bacteria / metabolism
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Humans
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Imidazoles / chemistry
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Inhibitory Concentration 50
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Pyridines / chemistry
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Staphylococcus aureus / metabolism
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Structure-Activity Relationship
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Topoisomerase II Inhibitors*
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Triazoles / chemistry
Substances
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Anti-Infective Agents
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Imidazoles
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Pyridines
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Topoisomerase II Inhibitors
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Triazoles
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Adenosine Triphosphatases
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DNA Topoisomerase IV