Date of Award

2025

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Timothy E Long

Second Advisor

Dr. Michael Hambuchen

Third Advisor

Dr. Hasan Koc

Abstract

Disulfiram (Antabuse) is an oral drug used for the treatment of alcohol dependence. Previous studies showed that disulfiram has antibiotic activity on multidrug-resistant bacteria. Here disulfiram was further evaluated for its ability to increase the potency of existing antimicrobials against the bacteria and yeast by acting as a drug adjuvant. Microbial cultures were treated with antibiotic or antifungal drugs in combination with disulfiram and its derivatives to determine whether potency is increased. The structure activity relationship (SAR) of disulfiram analogs was assessed against a triazole resistant Aspergillus panel. It showed that the shorter chained analogs of disulfiram are more potent against Aspergillus spp. In a separate study, this research examined whether disulfiram weakens bacteria to antibiotics. Bacterial cultures were re-exposed to disulfiram up to ten times then existing antibiotics were tested for potency. The increase in antibiotic potency gave evidence that disulfiram can lower the level of antibiotic resistance in bacteria. This is particularly evident with the decreased minimum inhibitory concentrations (MICs) for vancomycin (VAN) against the vancomycin-intermediate Staphylococcus aureus (VISA) and for ciprofloxacin and other fluoroquinolones against vancomycin-resistant enterococcus (VRE).

Subject(s)

Drugs -- Research.

Disulfiram.

Antibiotics.

Drug resistance in microorganisms.

Anti-infective agents.

Aspergillus.

Pharmacology.

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