Synthesis of ROS-activated anticancer prodrugs with increased sensitivity toward hydrogen peroxide
Our long-term goal is to develop selective anticancer drugs that can specifically kill cancer cells and are less toxic to normal cells. Our initial results showed that a prodrug of nitrogen mustard coupled with an arylboronate can be selectively activated by H2O2 to release the chemotherapy agent. Such agent showed selective toxicity toward cancer cell. The objective of this application is to design and synthesize more efficient H2O2-cleavable triggers and be coupling them with more potent effector. We plan to accomplish the objective of this application by pursuing two specific aims:
Aim 1: Synthesize novel prodrugs that can be activated by hydrogen peroxide to release multiple effectors, e.g. biqiunone methides and dual nitrogen mustards.
Aim 2: Determine the sensitivity and selectivity of the trigger units toward hydrogen peroxide using NMR analysis.