9-alkyl anthracyclines. Absence of cross-resistance to adriamycin in human and murine cell cultures.
Four cell lines of human (CCRF CEM and U266BL) or murine (L1210 and P388D1) origin, resistant to the anthracycline antibiotic Adriamycin (doxorubicin) were selected in vitro from cultured cells by serial passage in the presence of Adriamycin. The resistant sublines were also cross-resistant to Mitoxantrone, 4'-epi Adriamycin and a number of novel anthracyclines including 4'-deoxy and 4'-methoxy analogues. However, a series of 9-alkyl substituted 4-demethoxyanthracyclines retained full activity against all the resistant sublines as did Aclacinomycin A. These results suggest that 9-alkyl substitution of 4-demethoxy-anthracyclines is an important determinant of activity against Adriamycin-resistant cell lines in vitro.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin