Synthesis and antitumor activity of isodoxorubicin analogues.
The synthesis and biological activity of the new 4-demethoxyanthracyclines 15, 22, and 23 are reported. They were obtained from synthetic 9-deacetyl-9-(hydroxymethyl)-4-demethoxydaunomycinone (isopropylidene derivative 9) and from 4-azido- or 4-amino-2,4,6-trideoxy-L- lyxo-hexoses. Anthracycline 22 (hydrochloride salt), the most active compound in the series, was slightly more potent than doxorubicin in vitro against three cell lines (L1210, HT29, A549). It was found to exhibit similar antitumor activity in vivo (iv route) against L1210 leukemia, but was less active than doxorubicin against three human tumors in a subrenal capsule assay LXF, A549, and HT29).
Service de Chimie, CNRS, URA 1387, Institut Curie, Paris, France.
J C
JC
Florent
G
G
Gaudel
C
C
Monneret
D
D
Hoffmann
H P
HP
Kraemer
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002460:Cell Line; D004317:Doxorubicin / Q000031:analogs & derivatives*; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013234:Stem Cells / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin