Researchers predict that by 2050, bacterial infections will surpass both cancer and heart disease as the number one cause of death. The alarming increase in antibiotic-resistant bacterial infections demonstrates an urgent need for the development of new antibacterial materials. Many antibiotics currently available target a specific gene or enzyme to kill bacteria, and mutations in bacteria quickly develop to circumvent the activity of these antibiotics. Nitric oxide (NO) is an excellent alternative antimicrobial agent, as it exhibits multiple mechanisms of action to kill bacteria, making resistance much more difficult to develop. However, targeted drug delivery is necessary when using NO as a therapeutic, as it has several unrelated functions throughout the body. In addition, exposure of bacteria to antibiotics unnecessarily exacerbates the problem of antibiotic resistance. Both of these challenges can be addressed with an enzyme-activated NO prodrug that releases NO after exposure to a bacteria-specific enzyme. In this presentation, the synthesis of an enzyme-activated NO-releasing antibiotic prodrug will be discussed. It will be shown that NO release is exclusively in the presence of a bacteria-specific enzyme that metabolizes the NO prodrug to release NO. Bacteria will be exposed to the synthesized NO-releasing compound to determine if it causes a decrease in viable bacteria, indicating antibacterial activity. Applications of the synthesized antibacterial compounds to be added into polymer blends will be explored. These polymer blended materials could be used as coatings for medical devices to create devices that dispel bacterial infections as they form by releasing NO only when bacteria encounter the surface of the medical device.

Synthesis of a novel enzyme-activated nitric oxide prodrug for antibacterial applications

2019 Fall National Meeting

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