Mentor: Professor William Malachowski
In the human body, indoleamine-2-3-dioxygenase (IDO) catalyses the metabolism of tryptophan (an essential amino acid). It was found that in fetal cells without tryptophan, T cells were inhibited in their multiplication stages. The suppression of T cells is essential in preventing fetal rejection from the body’s immunological responses.
It has recently been found that some tumors express the enzyme IDO. This protects the tumors from the immunological activity of T cells, thereby resulting in the undisturbed growth and reproduction of tumor (cancer) cells.
An effective way to rectify this problem is to develop some form of inhibitor for the IDO enzyme. As such, the aim of my research this summer was to aid in the synthesis of potential IDO inhibitors.
Previously, the Malachowski group was focused on synthesizing tryptophan derivatives as IDO inhibitors. However, very recently, it was reported that the compounds annulin C, discovered by researchers at the University of British Columbia in marine sea sponge material, (Fig. A) and menadione (vitamin K3, Fig. B) , both naphthoquinone derivatives, are much more effective and potent inhibitors of IDO (KI values 144nm and 580nm respectively).
Therefore, we turned our attention to the synthesis of 1, 4-naphthoquinone derivatives (Fig. C) as possible IDO inhibitors.