Publications by authors named "Sophia Briet"
Article Synopsis
- Researchers optimized an HldE kinase inhibitor to a low nanomolar potency, discovering compounds that target specific E. coli strains.
- The standout candidate, compound 86, selectively inhibited the bacterial LPS heptosylation without affecting overall E. coli growth, while enhancing sensitivity to hydrophobic antibiotics and serum complement killing.
- These findings highlight HldE kinase as a promising target for new drugs, offering potential strategies to treat or prevent bloodstream infections caused by harmful Gram-negative bacteria.
In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.
View Article and Find Full Text PDFGram-negative bacteria lacking heptoses in their lipopolysaccharide (LPS) display attenuated virulence and increased sensitivity to human serum and to some antibiotics. Thus inhibition of bacterial heptose synthesis represents an attractive target for the development of new antibacterial agents. HldE is a bifunctional enzyme involved in the synthesis of bacterial heptoses.
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