Natural Product-Inspired Pyranonaphthoquinone Inhibitors of Indoleamine 2,3-Dioxygenase-1 (IDO-1)*

A series of pyranonaphthoquinone derivatives possessing structural features present in both natural products annulin B and exiguamine A have been shown to exhibit low micromolar inhibition of indoleamine 2,3-dioxygenase-1 (IDO-1). These inhibitors retain activity against the enzyme in a cellular context with an approximate one-log loss of dose potency against IDO-1 in cells. One particular analogue, triazole 8 shows good inhibition of IDO-1 along with little loss of cell viability at low drug concentrations. These results have extended the naphthoquinone series of novel IDO-1 inhibitors based on lead compounds from nature.