Developing a New Class of Antibiotics: The Oxadiazoles

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Authors

Houske, Eden
Blote, Emily
Doyle, Sophia

Date of Issue

2022

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en_US

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Bacterial antibiotic resistance is a significant issue that has persisted in healthcare due to bacteria's fast mutation rates which constantly drives the need for new therapeutic drugs. This includes the synthesis of novel antibiotics that hold promise in interfering with bacterial mechanisms of resistance (e.g. mutation). Recently, the synthesis of oxadiazole derivatives has been a specific area of interest as these non-B-lactam antibiotics appear to be strong candidates. In 2014, researchers reported a series of 1,2,4-oxadiazole antibiotics that were discovered through in silico screening in which a variety of structures were docked computationally to a protein target associated with bacterial resistance. After an initial oxadiazole structure showed promise, further synthetic refinement of the core structure resulted in a series of active antibiotic compounds of varying substitution. Although numerous candidates have been successfully synthesized previously, there is a lack of derivatives with varying substitution patterns on the phenyl rings, which may prove beneficial to increasing the potency of the oxadiazole-based compounds. Therefore, the aim of this study is to synthesize novel oxadiazole compounds that provide variations on the phenyl rings substituting the 3 and 5 positions of the 1,2,4-oxadiazole ring. These compounds could subsequently be tested for their antibiotic potencies to determine which structures are most effective in preventing bacterial proliferation. Thus far, a reported oxadiazole has been successfully synthesized in our lab, which will serve as a control. To date, several novel oxadiazoles not reported previously are one reaction away from the desired antibiotic form.

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