Targeting hypoxia with a new generation of indolequinones
Jaffar, M.; Naylor, M.A.; Robertson, N.; Stratford, I.J.
Anti-Cancer Drug Design 13(6): 593-609
1998
ISSN/ISBN: 0266-9536 PMID: 9755720 Document Number: 490122
The indolequinone class of bioreductive alkylating agents has been developed to effectively target the hypoxic cell population of the tumour. The mechanism of activation of these prodrugs relies initially on the reduction of the p-quinonoid moiety utilizing reductive enzymes to form electrophilic sites which can be attacked by DNA to promote cell kill. Minor structural changes of the indole 'nucleus' may result in substantial favourable pharmacological and physiological changes. Investigation of the mode of action of these compounds has resulted in the use of novel indolequinones as 'trigger' molecules that can efficiently release secondary agents into the hypoxic site of action.