CD437 was identified in a high-throughput <i>C. elegans</i> screen in the Mylonakis lab at Brown University. It was selected based on its ability to kill MRSA persister cells. Persister cells remain a significant challenge as they are increasingly resistant to treatment with antibiotics, in often already resistant strains (i.e. MRSA). The identified mechanism of action of the compounds is membrane intercalation, which permits bactericidal activity as well as synergistic effects with gentamicin. Unfortunately, the compounds exhibited high levels of toxicity. Our synthetic background was utilized in generating a library of analogs that would meet two qualifications: less toxic and more potent. This work explores a novel class of membrane-damaging antibiotics that do not induce cell lysis.<br/>

Synthesis of CD437 analogs: compounds with MRSA persister cell activity and antibiotic synergy

256th National Meeting (2018)

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