Preobrazhenskaya M N, Bakina E V, Povarov L S, Lazhko E I, Aleksandrova L G, Balzarini J, De Clercq E
Institute of New Antibiotics of the USSR Academy of Medical Sciences, Moscow.
J Antibiot (Tokyo). 1991 Feb;44(2):192-9. doi: 10.7164/antibiotics.44.192.
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.
