Cancer is a disease of uncontrolled cellular growth. This proliferation causes the cell to have a higher metabolism, expend more energy and have higher ambient levels of certain molecules, such as reactive oxygen species (ROS). ROS are chemically reactive molecules such as the superoxide anion, hydroxyl radicals, and hydrogen peroxide. One important function of ROS is to act as a signaling molecule in various intercellular signaling pathways, such as the one for cell growth. We and others have shown that it is possible to selectively target cancer cells using agents activated by ROS. The current literature shows the use of various pro-drug strategies like boronic ester derivatives and ferrocenes. These compounds upon oxidation by H<sub>2</sub>O<sub>2</sub> release electrophiles or metals which react with DNA and cause apoptosis. Work in Dr. Merino’s lab is focused on a different pro-drug strategy using hydroquinone scaffolds as the ROS acceptors. This ROS acceptor is connected to a linker and hydrophobic group that imparts selectivity in the action of these molecules. The lab is currently accomplishing a structure-activity relationship study to obtain a molecule with sub-micromolar activity and 10-fold selectivity. The goal is to understand the effect of chirality and size at the alpha carbon on this novel ROS-activated agent. Three, out of six, such compounds have been synthesized and are being tested for cytotoxicity against AML cell lines.

Structure activity relationship (SAR) studies of a selective reactive oxygen species (ROS) activated agent

251st National Meeting (2016)

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