Carminomycin, 14-hydroxycarminomycin and its novel carbohydrate derivatives potently kill human tumor cells and their multidrug resistant variants.
The new hydrophilic derivatives of 14-hydroxycarminomycin were obtained using 13-dimethyl ketal of 14-bromocarminomycin (6) as the starting compound. The reductive alkylation of 6 with melibiose or D-galactose followed by hydrolysis of the corresponding intermediate bromoketals 9 and 11 produced 3'-N-[-alpha-D-(galactopyranosyl-(1 --> 6)-O-D-1-desoxyglucit-1-yl]-14-hydroxycarminomycin (10) and 3'-N-(1-desoxy-D-galactit-1-yl)-14-hydroxycarminomycin (12), respectively. These novel derivatives 10 and 12 were less toxic than carminomycin or 14-hydroxycarminomycin for leukemia (K562) and breast carcinoma (MCF-7) cells. Importantly, carminomycin, 14-hydroxycarminomycin and compounds 10 and 12 were similarly active for wild type cells and their multidrug resistant (MDR) sublines, K562i/S9 and MCF-7Dox.
Tevyashova
Anna N
AN
Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, 11 B. Pirogovskaya, Moscow 119021, Russia.
Shtil
Alexander A
AA
Olsufyeva
Eugenia N
EN
Simonova
Valeria S
VS
Samusenko
Alexei V
AV
Preobrazhenskaya
Maria N
MN
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002360:Carubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002470:Cell Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C485089:14-hydroxycarminomycin; D018435:ATP Binding Cassette Transporter, Subfamily B; D000903:Antibiotics, Antineoplastic; D002360:Carubicin