Document Type
Article
Publication Date
Summer 9-1-2014
Abstract
Fatty acid synthase (FASN) is the enzyme that synthesizes fatty acids de novo in human cells. Although FASN is generally expressed at low levels in most normal tissues, its expression is highly upregulated in many cancers. Consistent with this notion, inhibition of FASN activity has demonstrated potential to halt proliferation and induce cell death in vitro and to block tumor growth in vivo. Consequently, FASN is widely recognized as a valuable therapeutic target. In this report, we describe a variety of 1,4-quinones and 9,10- anthraquinones, including several natural compounds and some newly synthesized compounds, that potently inhibit the thioesterase (TE) domain of FASN. Inhibition of recombinant TE activity, inhibition of cellular FASN, and cytotoxicity in human prostate cancer cell lines and normal fibroblasts, is shown for the most potent inhibitors. Collectively, the data illustrate the novel inhibitory capacity of the 1,4-quinone and 9,10- anthraquinone pharmacophores against FASN.
Recommended Citation
Odens, Herman H., "Inhibition of the Thioesterase Activity of Human Fatty Acid Synthase by 1,4- and 9,10-Diones" (2014). Faculty Works. 1.
https://knowledge.e.southern.edu/facworks_chem/1
Included in
Medicinal and Pharmaceutical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Natural Products Chemistry and Pharmacognosy Commons, Organic Chemistry Commons, Pharmaceutics and Drug Design Commons
Comments
Southern Adventist University
Wake Forest School of Medicine