Design, synthesis and biological activity of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo- hexopyranosyl)daunomycinone.
The synthesis and pharmacological evaluation of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo-hexopyrano syl) daunomycinone are described. Their cytotoxic activity was evaluated against normal and resistant cell lines. Both compounds exhibited activity against the adriamycin resistant cell line KB-A1. These results support the hypothesis that the increased lipophilicity of the sugar part of anthracyclines is associated with their ability to overcome multidrug resistance (MDR).
Aligiannis
N
N
University of Athens, Department of Pharmacy, Panepistimiopolis-Zografou, Greece.
Pouli
N
N
Marakos
P
P
Mitaku
S
S
Skaltsounis
A L
AL
Leonce
S
S
Pierre
A
A
Atassi
G
G
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D019450:Genes, MDR; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D014407:Tumor Cells, Cultured
C406443:7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-lyxo-hexopyranosyl)daunomycinone; C406442:7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-arabino-hexopyranosyl)daunomycinone; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin