A survey of data obtained from a variety of biological assays on a drug library consisting of more than 200 synthesized small organic molecules has revealed significant potential anticancer activity for molecules containing a specific structural motif. Previously, several of the compounds in a library of drugs, which were designed to activate the Wnt pathway (to promote stem cell pluripotency), were found to decrease β-catenin levels in cancer cells. In previous studies, it has been found that cancer cells show an increase of β-catenin levels, therefore, it is hypothesized that drugs which inhibit cancer cell growth are reducing β-catenin levels. The dysregulation of β-catenin led us to investigate the potential influence of these drugs on cell proliferation. Cell proliferation was determined by the CyQuant assay, which uses DNA content of the cells to quantify the number of plated cells. HeLa cells were treated with the drug (10 uM) for 24 hours and the DNA content was quantified. The TOPflash assay will be used to measure the levels of b-catenin in HeLa cells after exposure to the newly synthesized drugs. Preliminary results show that several drugs inhibit cell proliferation significantly, in some cases better than known anticancer drugs such as mitomycin C and cisplatin. Certain trends regarding the structure of the drug and the activity have been observed. For instance, longer alkyl chains on one part of the molecule in combination with a polar ester or ether group on the opposite part of the molecule show to reduce HeLa cell growth more efficiently than shorter alkyl chains. Further experiments have shown that the presence of two polar substituents on opposite sides of the drug does not reduce HeLa cell growth effectively. Further studies are currently underway to optimize the drug library with more efficient anti-cancer drugs and to determine the mechanism of action of these drugs.

Design and synthesis of drugs that reduce β-catenin and attenuate cell proliferation

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.