Doxorubicin prodrugs with reduced cytotoxicity suited for tumour-specific activation.
The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-nitrophenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronate (5) and doxorubicin. Their low cytotoxicity, efficient release of doxorubicin after hydrolysis by beta-D-glucuronidase, and in the cases of 2 and 3 stability at pH 7.2 fulfil the preliminary requirement for their use in antibody-directed enzyme prodrug therapy or prodrug monotherapy.
Desbène
S
S
Laboratoire de Pharmacognosie, URA au CNRS No. 1310, Paris, France.
Van
H D
HD
Michel
S
S
Koch
M
M
Tillequin
F
F
Fournier
G
G
Farjaudon
N
N
Monneret
C
C
D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006868:Hydrolysis; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D011355:Prodrugs; D004317:Doxorubicin