Modifying Heterocycles to Treat Gram Positive and Gram Negative Bacteria
Technical Report,01 May 2018,30 Apr 2019
University of Nebraska Medical Center Omaha United States
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Bacterial infections are a serious threat to human health. During the award period we focused on the synthesis of some phenazines with potential antimicrobial activity. Our hypothesis is the conjugation of amines, polyamines and peptides to the phenazines will enhance their activity. We achieve the synthesis of several new phenazines containing diverse functional groups. Most of the new compounds presented modest antibacterial activity, thus, a structural optimization is being performed using the obtained data. The attachment of amines to the active phenazines proved difficult due to a rearrangement that took places. Thus, we focused in optimizing the structure of potential peptides that can be added to the phenazines. We prepared and evaluated some intriguing new peptides that presented potent activity against a panel of gram positive and gram negative pathogens. We also identified some key features that give rise to their activity. Over the next year we will focus on creating phenazine-peptide conjugates as novel antibacterials.