Author ORCID Identifier

0000-0002-7763-0380

Date of Award

Fall 12-13-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Binghe Wang

Abstract

Multi-drug resistant (MDR) bacteria is one of the major health threats to public health. The rate of development of antibiotics is unable to keep pace with the rate of emergence of MDR bacteria. Thus, there is an urgent need to find a way to make existing antibiotics effective again against these MDR strains. Along this line, we have developed compounds that sensitize Gram-negative strains towards various existing antibiotics, both broad- and narrow-spectrum. These compounds work by disrupting the outer membrane of Gram-negative bacteria. These sensitizers exhibit a much lower tendency to induce resistance in bacteria than commonly used antibiotics.

Mitochondria, the powerhouse of the cell, is involved in various disease states apart from diseases related to DNA or nuclear gene mutation. Metabolic diseases, ischemia-reperfusion injuries, neurodegeneration and cancer are some of the few pathological conditions where mitochondria can act as a drug target site.1 At present, alkyl triphenylphosphonium is generally used as a lipophilic cation through covalent conjugation to the drug of interest to achieve selective mitochondrial delivery.2-4 A major drawback of this approach is the toxicity of the triphenylphosphine moiety.5, 6 There is a need to explore more clinically relevant and relatively benign targeting moieties in order to achieve mitochondrial selectivity in animal models. Along this line, we explore the possibility of using lutidinium as a targeting moiety.

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