Zidu Zeng
Department of Chemistry
Advisor: Dr. Bill Malachowski

Indoleamine 2,3-dioxygenase inhibitor design and synthesis

My research project is currently targeting the synthesis of a new structural class of IDO enzyme inhibitors for the treatment of cancer. Due to the fact that tumors are capable of escaping immune control during their development, and IDO enzyme was found to enable these immune escape events, the study and synthesis of IDO enzyme inhibitors is critical to help the body reverse the immune system suppression that enables cancer’s growth.

To date, the Malachowski group has synthesized three IDO enzyme inhibitor structural classes that can be used as potential drugs for cancer treatment. During this summer, the Malachowski group is focusing on the synthesis of a new IDO inhibitor that will hopefully react with IDO via covalent or irreversible inhibition.The new inhibitor uses knowledge about the enzyme mechanism and, in particular, the radicals formed during the IDO catalyzed reaction to undermine the normal process.  To accomplish this, the synthesis of an indole derivative that contains a cyclopropane ring will be undertaken. A series of chemical reactions, including a tosylation reaction, a Wittig reaction, a cyclopropanation reaction, and a saponification reaction will be done. The effectiveness of these inhibitors in reducing IDO’s catalytic activity will be tested by our collaborators at Albert Einstein College of Medicine.