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As a Cell and Molecular major with a Pre-Pharmacy emphasis, medicine has been an interest of mine. The major cause of increasing bacterial resistance to beta-lactam antibiotics is due to the expression of the enzyme beta-lactamase in bacteria. This leads to the inactivation of the antibiotics and preventing cell death. The currently known inhibitors of beta-lactamase are clavulanic acid, sulbactam, and tazobactam. These are the only inhibitors that have reached clinical importance. Phthalic acids derivatives have been identified as potential inhibitors. Phthalic acid, Terephthalic acid, and 1,2-Phenylenediacetic acid were tested for beta-lactamase inhibition at various concentrations to determine the IC50 values. The data showed that terephthalic acid was the most inhibitory of beta-lactamase. The IC50 for terephthalic acid was not fully determined, however the smallest concentration of terephthalic acid tested,1.5 mM, yielded a beta-lactamase activity of 34%, in other words an 66% inhibition. The IC50 values for phthalic acid and 1,2-Phenylenediacetic acid were 8.0 +/- 0.6 mM and 2.8 +/- 0.8 mM, respectively. Phthalic acid and 1,2-Phenylenediacetic acid are both similar in structure and inhibition of beta lactamase. Terephthalic is the most different with its carboxyl groups spread out the furthest. This could point towards the distance of the carboxyl groups having a greater impact on inhibition of beta-lactamase. Although all three phthalic acid derivatives showed the ability to inhibit b-lactamase, it is unlikely that these molecules would make it to the clinical level due to the high concentration of each molecule needed to inhibit beta-lactamase activity. Clinical drugs used are in the concentration of nanomolar while this experiment showed that millimolar concentrations were necessary for inhibition. In the future, I hope another student continues this research and takes a further look into the effect of the distance of the carboxyl group has on the inhibition of beta-lactamase activity.

Content Notes

Research Report, Poster, Final Report Form

First Advisor

Myoung Lee



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