Halogenated indole-3-acetic acids as oxidatively activated prodrugs with potential for targeted cancer therapy.
Substituted indole-3-acetic acid (IAA) derivatives, plant auxins with potential for use as prodrugs in enzyme-prodrug directed cancer therapies, were oxidised with horseradish peroxidase (HRP) and toxicity against V79 Chinese hamster lung fibroblasts was determined. Rate constants for oxidation by HRP compound I were also measured. Halogenated IAAs were found to be the most cytotoxic, with typical surviving fractions of <10(-3) after incubation for 2h with 100 microM prodrug and HRP.
Gray Cancer Institute, PO Box 100, Mount Vernon Hospital, Northwood, HA6 2JR, Middlesex, UK. s.rossiter@ucl.ac.uk
Sharon
S
Rossiter
Lisa K
LK
Folkes
Peter
P
Wardman
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D006219:Halogens / Q000737:chemistry*; D006735:Horseradish Peroxidase / Q000378:metabolism; D007210:Indoleacetic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006219:Halogens; D007210:Indoleacetic Acids; D011355:Prodrugs; C030737:indoleacetic acid; D006735:Horseradish Peroxidase