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• W2346256483 abstract "Fatty acid biosynthesis is essential to bacterial growth in Gram-negative pathogens. Several small molecules identified through a combination of high-throughput and fragment screening were cocrystallized with FabH (β-ketoacyl-acyl carrier protein synthase III) from Escherichia coli and Streptococcus pneumoniae. Structure-based drug design was used to merge several scaffolds to provide a new class of inhibitors. After optimization for Gram-negative enzyme inhibitory potency, several compounds demonstrated antimicrobial activity against an efflux-negative strain of Haemophilus influenzae. Mutants resistant to these compounds had mutations in the FabH gene near the catalytic triad, validating FabH as a target for antimicrobial drug discovery." @default.
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• W2346256483 date "2016-05-09" @default.
• W2346256483 modified "2023-10-17" @default.
• W2346256483 title "Antibacterial FabH Inhibitors with Mode of Action Validated in <i>Haemophilus influenzae</i> by in Vitro Resistance Mutation Mapping" @default.
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• W2346256483 doi "https://doi.org/10.1021/acsinfecdis.6b00053" @default.
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