Niclosamide, an FDA approved drug for the treatment of parasites, which functions by uncoupling their mitochondria, has recently been repurposed as an effective anti-cancer drug therapy that is currently undergoing clinical trials. Previous research has shown that Niclosamide has great potential in reducing cell growth indiscriminately in cervical, epithelial, and osteosarcoma cancer cell lines. Previous work in our laboratory has indicated that certain ester groups show promise when used on small organic molecules used to reduce cell growth. Using Niclosamide as a starting point, a drug library consisting of these small organic molecules containing at least one type of ester substituent as well as a combination of bulky polar and non-polar groups were synthesized and tested in biological assays on HeLa, HUTU80, and MG63 cancer cell lines. The design of these compounds has taken into account their ability to effectively diffuse through the cell membrane and reach the target of interest as well as their specificity to one cancer cell line rather than all of the cell lines. The biological assays specifically focused on the drugs' ability to reduce cell growth in one or two, but not all of the cell lines. As an initial screening test, the CyQUANT® Cell Proliferation Assay (a fluorescence-based method for quantifying cells and assessing cell proliferation and cytotoxicity) was conducted using HeLa cells that have been inoculated with 10µM of a drug solution and allowed to incubate for a 24 hour period before collecting the data. This assay is utilized as a quick way to quantify drug efficacy in how well cancer growth is reduced and has helped to identify several promising leads. However, further assays and follow-up studies are needed in order to determine the importance of the ester group(s), the substituent(s), as well as their relative positions. This data, in turn, will help improve the design and performance of the new drug library.<br/>

Comparison of the efficacy of ester substituents in their specificity and effectiveness for reducing cell growth in certain cancer cell lines

253rd National Meeting (2017)

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