Synthesis and cytostatic properties of daunorubicin derivatives, containing N-phenylthiourea or N-ethylthiourea moieties in the 3'-position.
A series of phenylthiourea and ethylthiourea derivatives of daunorubicin and its congeners was prepared by reaction of the 3'-amino group of the antibiotic with phenylisothiocyanate or ethylisothiocyanate. S-Methylation yielded S-methylisothiouromium salts which when reacted with amines resulted in an intramolecular cyclization with the participation of the neighboring 4'-OH group. The structures and predominant conformations of the thiourea derivatives and daunorubicino(3'-N,4'-O-d)oxazolines were determined by 1H and 13C NMR. Cytostatic activities of the thiourea and oxazoline derivatives were compared with the cytostatic activities of N-methylurea and N-methyl-N-nitrosourea containing daunorubicin and its congeners. Carminomycin derivatives were endowed with the highest cytostatic activity.
Preobrazhenskaya
M N
MN
Institute of New Antibiotics of the USSR Academy of Medical Sciences, Moscow.
Bakina
E V
EV
Povarov
L S
LS
Lazhko
E I
EI
Aleksandrova
L G
LG
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003630:Daunorubicin / Q000031:analogs & derivatives*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010670:Phenylthiourea / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C068093:N-ethylthiourea; D010670:Phenylthiourea; D013890:Thiourea; D003630:Daunorubicin