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Synthesis and evaluation of Fusobacterium nucleatum FabK inhibitors as microbiome-sparing chemotherapeutic agents

Research Summary: There is a critical unmet need for the discovery of narrow-spectrum antibacterial agents with focused activity against the F. nucleatum pathogen. Specifically, in collaboration with Dr. Kirk Hevener at University of Tennessee Health Science Center (UTHSC) and Dr. Julian Hurdle at Texas A&M, we aim to design and synthesize a panel of small molecule analogs for anti-F. nucleatum and FabK evaluation in an effort to discover selective and potent microbiome-sparing chemotherapeutic agents. This will help us to understand what the structural requirements are to achieve selectivity for Fn, while generating research tools for advanced drug discovery. We will optimize the activity of current FnFabK inhibitors and to identify new inhibitors with novel chemotypes. Compounds will be tested for activities in FnFabK enzymatic assays, and against various F. nucleatum strains and commensal gut flora.

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