Shorouk Badir

Professor William P. Malachowski

Chemistry Department

Indoleamine 2,3-dioxygenase (IDO) Synthesis

The indoleamine 2,3-dioxygenase (IDO) enzyme inhibitors have demonstrated substantial therapeutic potential towards cancer.  An IDO inhibitor is a small molecule that hinders IDO, an enzyme known for driving immune escape, from inappropriately switching on in the presence of developing tumors.  To date, the Malachowski lab has synthesized, optimized, and explored the properties of three structural classes of IDO inhibitors: dithiocarbamates, naphthoquinones, and the phenyl-imidazoles. The focus of my research this summer is to synthesize a variety of other potential IDO inhibitors, including more phenyl-imidazole derivatives, sulfonamide, phthalimide and hydroxylamine compounds. In designing the new inhibitors, we are hoping to exploit known nucleophilic groups in the active site and large distal pockets that have recently been utilized to make more potent IDO inhibitors. The synthesis of the inhibitors will involve a wide range of chemical transformations including acylation processes, the Mitsunobu reaction and cross-coupling reactions. The successfully synthesized compounds will be sent to our collaborators at the Lankenau Institute of Medical Research for further investigation on their effect on the IDO enzyme, IDO activity in cell cultures and potentially their impact on mice tumors.