Publication Date


Document Type


First Advisor

Hagen, Timothy J.

Degree Name

M.S. (Master of Science)

Legacy Department

Department of Chemistry and Biochemistry


Invasive fungal species provide a challenge to the current drug landscape, only partiallymet by approved drugs. The Acetyl Coenzyme Synthetase (ACS) enzymes are an attractive target for antifungal compounds because normal mammalian cells do not rely on ACS for energy metabolism while fungal cells do rely on ACS. This work focuses on the design and synthesis of inhibitors of various fungal ACS enzymes. The first class of inhibitors is based on the 2-aminothiazole scaffold originating from a saturation transfer difference (STD) nuclear magnetic resonance (NMR) study and previous whole-organism assays. Ultimately, the 2-aminothiazole core compounds were found to not be potent inhibitors of fungal ACS enzymes. The second class of inhibitors were the diacylhydrazides. This series was based on selected compounds from the Medicines for Malaria Venture (MMV), which were studied against Plasmodium falciparum ACS enzyme. A homology study indicated that the same compounds could potentially inhibit fungal ACS in a similar manner, which was later found to not be the case. The synthesized compounds were tested against P, falciparum ACS and found to have some inhibitory activity. The third class of compounds were based on a Celecoxib derivative, AR-12, which was previously found to have antifungal, antibacterial, and antiviral activity. This compound was found to inhibit the ACS1 enzymes of various fungal species, and several analogs of AR-12 were synthesized in an effort to increase this activity.


101 pages




Northern Illinois University

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Available for download on Monday, June 16, 2025