Prodrugs of anthracycline antibiotics suited for tumor-specific activation.
The two novel prodrugs 4 and 11 have been prepared from tetra-O-acetyl-D-galactopyranose and doxorubicin in three and six steps, respectively. Their low cytotoxicity, high stability in plasma and, in the case of 11, efficient hydrolysis in the presence of alpha-galactosidase, fulfill preliminary conditions for their use in combination with monoclonal antibody-enzyme conjugates.
Azoulay
M
M
Institut Curie, Section Biologie, Paris, France.
Florent
J C
JC
Monneret
C
C
Gesson
J P
JP
Jacquesy
J C
JC
Tillequin
F
F
Koch
M
M
Bosslet
K
K
Czech
J
J
Hoffman
D
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000633:toxicity; D004317:Doxorubicin / Q000737:chemistry*; D005697:Galactosides / Q000737:chemistry; D007939:Leukemia L1210; D011355:Prodrugs / Q000737:chemistry* / Q000633:toxicity; D014407:Tumor Cells, Cultured; D000519:alpha-Galactosidase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D005697:Galactosides; D011355:Prodrugs; D004317:Doxorubicin; D000519:alpha-Galactosidase