Urdamycins, new angucycline antibiotics from Streptomyces fradiae. V. Derivatives of urdamycin A.
Derivatives of the angucycline urdamycin A (1) were prepared in order to study structure-activity relationships in this group of antitumor antibiotics. Derivatives of 1 formed by methanolysis, O-acylation, hydrogenation and treatment with diazomethane were isolated and characterized by their spectroscopic data. Urdamycin G (20) was isolated from Streptomyces fradiae by shortening the fermentation time. The different glycosidation pattern of the aglycone 14 did not lead to significant differences in the biological activity. O-Acylation was shown to enhance the in vitro activity of 1 against stem cells of murine L1210 leukemia depending on the lipophilicity of the molecules. The importance of the 5,6-double bond of 1 with regard to the antitumor activities is discussed.
Henkel
T
T
Institut für Organische Chemie, Universität Göttingen, FRG.
Ciesiolka
T
T
Rohr
J
J
Zeeck
A
A
D000107:Acetylation; D000215:Acylation; D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013302:Streptomyces / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014410:Tumor Stem Cell Assay; D000095602:Angucyclines and Angucyclinones
D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; C046608:kerriamycin B; D000095602:Angucyclines and Angucyclinones