Eliana Marciano

Cancer requires a great deal of energy to survive and grow, utilizing major metabolic pathways such as glycolysis or oxidative phosphorylation. Niclosamide is an old FDA approved antihelminthic that targets the mitochondria and has recently been shown to be effective in inhibiting cancer cell growth and inducing apoptosis. By creating a library of niclosamide derivatives that could potentially have increased solubility and bioavailability, niclosamide could be made more potent as an anticancer agent. In addition, squaramides have also shown success when utilized in chemotherapies due to the inhibition of NAD+ available for cancer cells. Squaramides are bioisosteres of ureas, which have been utilized in FDA approved anticancer agents such as sorafenib, and shown good prognosis in the treatment of cancer patients. Because ureas have had a good track record of anticancer properties, combining niclosamide with bioisostere squaramide could increase the potency of the niclosamide derivatives. By also utilizing various heterocyclic amines, the solubility of the squaramide conjugated derivatives could be increased. The derivatives will be evaluated for their in vitro cell proliferation inhibition properties using an MTT colorimetric assay. The most potent derivative will be assessed for its effect on targeting cells using Seahorse XFe Bioanalyzer. This project will determine if the addition of various amine heterocycles to niclosamide using the squaramide bioisostere will increase the anticancer potency and solubility of these derivatives compared to niclosamide.