Abstract
Analogs of CPZEN-45, which is expected to be a promising new antituberculosis drug that overcomes the shortcomings of caprazamycins, were synthesized and their biological activities were evaluated. The biological activity of analogs 1-3, which converted the anilide portion, and analogs 4 and 5, focusing on the seven-membered ring, were lower than that of CPZEN-45. These results suggest that the inhibitory activity of CPZEN-45 against TagO, an ortholog of WecA, has a strict structural limitation, and it was hoped for elucidation of the mode of action of CPZEN-45 using structural biology in the future.
MeSH terms
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Antitubercular Agents / chemical synthesis*
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology*
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Azepines / chemistry*
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Bacillus subtilis / drug effects
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Bacillus subtilis / enzymology
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Bacillus subtilis / genetics
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Escherichia coli Proteins / antagonists & inhibitors
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Microbial Sensitivity Tests
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Molecular Structure
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Mycobacterium / drug effects*
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Structure-Activity Relationship*
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Transferases (Other Substituted Phosphate Groups) / antagonists & inhibitors
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Transferases / antagonists & inhibitors
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Transferases / genetics
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Transferases / metabolism
Substances
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Antitubercular Agents
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Azepines
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Bacterial Proteins
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CPZEN-45
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Escherichia coli Proteins
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Transferases
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Transferases (Other Substituted Phosphate Groups)
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wecA protein, E coli
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mraY protein, Bacteria