Maggiemycin and anhydromaggiemycin: two novel anthracyclinone antitumor antibiotics. Isolation, structures, partial synthesis and biological properties.
Two new anthracyclinone antitumor antibiotics, maggiemycin (6, NSC-D344012) and anhydromaggiemycin (8) have been isolated from a culture of an unspeciated Streptomyces (ATCC No. 39235). Bioautography against Bacillus subtilis was used for the preliminary detection of these anthracyclinones. Structures were proposed based on their UV-visible, IR, 1H NMR, 13C NMR spectra, electron impact (EI) and high-resolution EI-MS and confirmed by partial synthesis and a direct correlation with epsilon-rhodomycinone. Both the anthracyclinones are active against KB, P388 and L1210 murine tumor cell lines; however, anhydromaggiemycin was more active than maggiemycin. A number of related anthracyclinones have also been prepared and their biological activity has been determined. The structure-activity relationship of these new anthracyclinones is also discussed.
Pandey
R C
RC
NCI-FCRF Fermentation Program, NCI-Frederick Cancer Research Facility, Maryland 21701.
Toussaint
M W
MW
McGuire
J C
JC
Thomas
M C
MC
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004354:Drug Screening Assays, Antitumor; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009279:Naphthacenes; D013053:Spectrophotometry; D013302:Streptomyces / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C015490:rhodomycinone; C061866:maggiemycin; C061867:anhydromaggiemycin; C019318:daunomycinone