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Synthesis of 1,2-Azaborines and the Preparation of Their Protein Complexes with T4 Lysozyme Mutants
Published on: March 25, 2017
Design, Synthesis, and Antifungal Activity of 3-Substituted-2(5H)-Oxaboroles
Rose Campbell1, Nicklas W Buchbinder1, Connor Szwetkowski1
1Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, United States.
Abstract:
Next generation antimicrobial therapeutics are desperately needed as new pathogens with multiple resistance mechanisms continually emerge. Two oxaboroles, tavaborole and crisaborole, were recently approved as topical treatments for onychomycosis and atopic dermatitis, respectively, warranting further studies into this privileged structural class. Herein, we report the antimicrobial properties of 3-substituted-2(5H)-oxaboroles, an unstudied family of medicinally relevant oxaboroles. Our results revealed minimum inhibitory concentrations as low as 6.25 and 5.20 μg/mL against fungal (e.g., Penicillium chrysogenum) and yeast (Saccharomyces cerevisiae) pathogens, respectively. These oxaboroles were nonhemolytic and nontoxic to rat myoblast cells (H9c2). Structure-activity relationship studies suggest that planarity is important for antimicrobial activity, possibly due to the effects of extended conjugation between the oxaborole and benzene rings.
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