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dc.contributor.advisorJohnson, Michaelen_US
dc.contributor.authorMistry, Tina L.en_US
dc.date.accessioned2017-02-17T19:07:54Z
dc.date.available2017-02-17T19:07:54Z
dc.date.created2016-12en_US
dc.date.issued2016-08-26en_US
dc.date.submittedDecember 2016en_US
dc.identifier.urihttp://hdl.handle.net/10027/21583
dc.description.abstractThis dissertation includes work on three projects. The first project was focused on conducting a high-throughput screen (HTS) with a 25000 compound library to discover inhibitors of the PurC enzyme from S. pneumoniae. In addition to optimizing the malachite green assay for high throughput screening, a compound interference assay was also used to eliminate false positive HTS hits with a single step. This method was also validated by a 93% agreement in results from the interference assay and the continuous pyruvate kinase/lactate dehydrogenase assay, which was used as a secondary assay for hit validation. The second project describes the characterization of a previously published series of benzimidazole-based inhibitors of the FabI enzyme from F. tularensis (FtFabI) to evaluate their potential for anti-staphylococcal drug discovery. A preliminary structure-activity relationship (SAR) study showed that some of the benzimidazole-based compounds are potent inhibitors of S. aureus FabI (SaFabI). Important SaFabI residues that are critical for the inhibitory activity of these compounds have been identified through mutagenesis studies. This work also confirms that the observed antibacterial activity of three of the benzimidazole-based SaFabI inhibitors from this preliminary series, is a result of direct FabI inhibition (on-target effect). The third project evaluated the potential of the benzimidazole-based compounds for developing anti-malarials. Contrary to the hypothesis, these benzimidazole-based inhibitors of FtFabI and SaFabI were found to be inactive against the FabI enzyme from Plasmodium falciparum. A potential reason for this lack of observed activity has been discussed to drive this project further in the future.en_US
dc.format.mimetypeapplication/pdfen_US
dc.rightsCopyright 2017 Mistry, Tina
dc.subjectPurCen_US
dc.subjectHTSen_US
dc.subjectmalachite greenen_US
dc.subjectFabIen_US
dc.subjectmechanism of actionen_US
dc.subjectS. aureusen_US
dc.titleSpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabIen_US
dc.typeThesisen_US
thesis.degree.departmentMedicinal Chemistry and Pharmacognosyen_US
thesis.degree.disciplineMedicinal Chemistryen_US
thesis.degree.grantorUniversity of Illinois at Chicagoen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhD, Doctor of Philosophyen_US
dc.contributor.committeeMemberFung, Leslieen_US
dc.contributor.committeeMemberBurdette, Joannaen_US
dc.contributor.committeeMemberMurphy, Brianen_US
dc.contributor.committeeMemberGaponenko, Vadimen_US
dc.type.materialtexten_US
dc.contributor.chairJohnson, Michaelen_US


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