Date Approved

4-16-2019

Embargo Period

4-29-2019

Document Type

Thesis

Degree Name

MS Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

First Advisor

Perez, Lark

Second Advisor

Jonnalagadda, Subash

Third Advisor

Keck, Thomas

Subject(s)

Antibacterial agents; Drug development

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

Quorum Sensing (QS), a form of bacteria communication mediated through chemical signaling, was investigated in the bacterial pathogen Pseudomonas aeruginosa. QS has the ability to regulate when a bacterial pathogen is infective or benign. LasR is the main regulator in this system and is also the receptor targeted for inhibition. A Structure Activity Relationship was produced for the system along with the binding pocket being explored.

A new reaction methodology was developed inspired by the Haloform reaction. The reaction was optimized based on solvent, stoichiometry, and conditions. Changing the initial electrophile and the reagent nucleophile created the scope of the reaciton.

A series of molecules were prepared as Narrow Spectrum Antibiotics against both Pseudomonas aeruginosa and Acinetobacter baumannii. A Structure Activity Relationship was created for these molecules testing three key positions of the structure with steric and electronic changes. Optimization of the molecule leads to a potentially new lead compound in the series. Future directions for the molecule are discussed in order to further expand the SAR while also increasing the stability of the molecules, and possibly reducing toxicity.

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