Targeting hypoxia with a new generation of indolequinones.
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.
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, UK.
M
M
Jaffar
M A
MA
Naylor
N
N
Robertson
I J
IJ
Stratford
D000970:Antineoplastic Agents; D001388:Aziridines / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects*; D006801:Humans; D045563:Indolequinones; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; D007211:Indoles; D011809:Quinones; D010088:Oxidoreductases; C060817:apaziquone