Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a Gram-positive, opportunistic pathogen that causes soft tissue and systemic infection in humans, accounting for 80,000 invasive infections and 11,285 related deaths annually. Because of the rapid development of genetically encoded resistance mechanisms in MRSA and other multi-drug resistant pathogens, a new approach to addressing and treating bacteria is needed. One such approach is the development of adjuvant therapies, non-toxic compounds which repotentiate the therapeutic effects of antibiotics. We have recently described a class of structurally similar dibenzoxazepines that are capable of disarming MRSA resistance mechanisms and restoring the efficacy of β-lactam antibiotics. The structure-activity profile of the dibenzoxazepines is being explored as a scaffold for potential adjuvant therapies. Synthesis and evaluation of a focused analog library to probe expansions to the core dibenzoxazepine ring and extracyclic amine group to construct a more complete structure-activity profile has been initiated. Synthetic efforts, biological results, and preliminary structure-activity analyses will be presented.

Synthesis and evaluation of a focused analog library with β-lactam antibiotic potentiation activity in methicillin-resistant <i>Staphylococcus aureus</i>

255th National Meeting (2018)

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Synthesis and evaluation of a focused analog library with β-lactam antibiotic potentiation activity in methicillin-resistant Staphylococcus aureus