Chalcones are a,b-unsaturated ketone bearing natural products found in variety of plants. Also, chalcones are key intermediates in the biosynthesis of flavonoids and isoflavonoids, and historically known to exhibit anti-cancer, anti-oxidant, anti-inflammatory, anti-viral, anti-bacterial, anti-malarial, and radical scavenger activities. We report synthesis of a study of 25 synthetic chalcone derivatives and their anti-proliferative activities in the sixty human tumor cell lines. The phenotypic screening identified three ‘hit’ chalcones which showed potent anti-cancer activity in various cancer cell lines, including the triple negative breast cancer (TNBC) cell lines MDA-MB-231 and MDA-MB-468. Quantitative proteomics experiments were performed using mass spectrometry to identify key pathways affected by these ‘hit’ compounds in these TNBC cell lines. Results showed an increase in the abundances of proteins involved in the G2/M and S phases of the cell cycle and a decrease in the abundances of tubulins, which form the microtubule spindle essential for cell division. This data suggests that the compounds act by induction of cell cycle arrest, leading to apoptosis. Details on the synthesis, anti-cancer screening, proteomics, and validation will be presented.

Novel chalcone derivatives as potential therapeutic agents for triple negative breast cancer

256th National Meeting (2018)

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