Synthesis and cytostatic activity of the antitumor antibiotic chartreusin derivatives.
In order to overcome the rapid biliary excretion of chartreusin, which diminished its activity when administered iv, a series of 3',4'-O-substituted derivatives of chartreusin were synthesized. Exo-type of 3',4'-O-benzylidene-chartreusin was found active both by ip and iv administration. Therefore, this compound was selected for further modification on its 6-phenol to obtain broader spectra and better pharmacokinetic parameters than the original compound. Several 6-O-acyl-3',4'-O-exo-benzylidene-chartreusins had high antitumor activity against some murine tumors both by iv and po administration.
Kon
K
K
Biochemistry Research Laboratory, Ishihara Sangyo Kaisha, Ltd., Shiga-ken, Japan.
Sugi
H
H
Tamai
K
K
Ueda
Y
Y
Yamada
N
N
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000627:therapeutic use; D001578:Benzopyrans; D055598:Chemical Phenomena; D002621:Chemistry; D006027:Glycosides; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001578:Benzopyrans; D006027:Glycosides; C064492:3',4'-O-benzylidene-chartreusin; C002185:chartreusin