Targeting hypoxia with a new generation of indolequinones

The indolequinone class of bioreductive alkylating agents has been develope d to effectively target the hypoxic cell population of the tumour. The mech anism of activation of these prodrugs relies initially on the reduction of the p-quinonoid moiety utilizing reductive enzymes to form electrophilic si tes which can be attacked by DNA to promote cell kill. Minor structural cha nges of the indole 'nucleus' may result in substantial favourable pharmacol ogical and physiological changes. Investigation of the mode of action of th ese compounds has resulted in the use of novel indolequinones as 'trigger' molecules that can efficiently release secondary agents into the hypoxic si te of action.