Publication Date
2023
Document Type
Dissertation/Thesis
First Advisor
Hagen, Timothy J.
Degree Name
M.S. (Master of Science)
Legacy Department
Department of Chemistry and Biochemistry
Abstract
Pathogenic fungi pose a severe threat to patients in developing countries. Although these fungi claim the lives of millions every year, modern healthcare is sorely lacking in ways to control them. This work will explore the development and synthesis of four series of compounds with potential antifungal activity via inhibition of ACS1. The first is based on a thienopyrimidine moiety and was discovered in a screen of compounds from the Hagen Group’s in-house compound library. Analogs in this series demonstrated some degree of improvement in activity over the lead compound, but they were held back by solubility issues and poor activity overall. The second is based on two known inhibitors of malarial ACS1 obtained from the Medicines for Malaria Venture (MMV), one based on an aminothiazole hydrazone core and the other on a benzothiazole core. Unfortunately, neither subset of analogs synthesized in this series demonstrated greater inhibition than their respective lead compounds. The third is indirectly based on the proposed anticancer agent AR-12, which was found to exhibit broad-spectrum antifungal activity and potent competitive inhibition of S. cerevisiae ACS1. This series is composed of analogs of celecoxib and is based on a 1,5-arylpyrazole core. Finally, the last series which will be investigated is derived from a compound originally purchased from Chembridge Corporation. This work is still in its preliminary stages but has already shown intriguing results and has great prospects for future work
Recommended Citation
Jones, Theodore Cormac, "Design and Synthesis of Acetyl CoA Synthetase-1 Inhibitors" (2023). Graduate Research Theses & Dissertations. 7827.
https://huskiecommons.lib.niu.edu/allgraduate-thesesdissertations/7827
Extent
158 pages
Language
en
Publisher
Northern Illinois University
Rights Statement
In Copyright
Rights Statement 2
NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.
Media Type
Text
