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 the β-catenin levels in the cell. The dysregulation of β-catenin has also been linked to various types of cancer and we therefore decided to investigate the potential influence of these drugs on cell proliferation. The drugs tested in the assays consisted of compounds containing chalcones, amines, amides, small peptides, esters, aldehydes, ketones as well as oximes and oxime ether functionalities. 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 μM) for 24 hours and the DNA content was quantified. Preliminary results show that several drugs inhibit cell proliferation significantly, in some cases even better than known anticancer drugs such as mitomycin C and cisplatin. Further studies are currently underway to determine the mechanism of action underlying the anti-proliferative effect of these drugs. A structure-activity analysis of the most active drugs suggests that many of them have an amide linker as a common functionality. Further work is underway to expand the drug library in order to find more potent drugs.

Synthesis and structure-activity studies of drugs that affect a cancer causing mechanism and reduce cell growth

249th National Meeting (2015)

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