Reactive Oxygen Species (ROS) are chemically reactive molecules formed as a natural byproduct of metabolism in cells. These species play an important role in cell signaling and homeostasis. Recent literature studies have shown that bulk cancer cells, including cancer stem cells, have elevated levels of ROS when compared to normal cells. Based on the literature support, our lab is designing novel ROS activated pro-drugs that target cancer cells over normal cells. We recently synthesized a new scaffold which undergoes oxidation in presence of ROS to activate. We hypothesize that these new agents upon oxidation, undergo addition reaction via Michael chemistry, thus reacting with anti-oxidants in the cell to cause its depletion leading to cell death. Synthesis of a new series of these agents with modifications at various locations in the parent molecule (SAR analysis) has revealed the importance of an amine that imparts selectivity towards specific cancer cell line. One such hit novel agent has shown >10 fold selectivity when compared to normal blood cells. Here I will be discussing the synthesis and strategies of ROS-activated molecules and how ROS-activation can be used for development of new pro-drugs for efficient and selective treatment of cancers.

Novel ROS-activated quinone prodrugs: A new strategy for tumor-specific damage

248th National Meeting (2014)

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