Bioorganicheskaia khimiia 1990-04-01

[Derivatives of antineoplastic antibiotics of the daunorubicin series containing methylurea or nitrosomethylurea residues].

L S Povarov, E V Bakina, E I Lazhko, G I Orlova, O S Zhukova, N A Obidniak, G I Iurchenko, T Iu Glazkova, M N Preobrazhenskaia

Index: Bioorg. Khim. 16(4) , 559-68, (1990)

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Abstract

Derivatives of antitumour anthracycline antibiotics containing N-methylurea moiety in the carbohydrate ring were obtained by the interaction of methyl isocyanate with daunorubicin, doxorubicin, carminomycin and daunorubicin derivatives, substituted at C-13 or C-14 positions. N-Nitrosation of these compounds yielded modified anthracycline antibiotics containing the N-methyl-N-nitrosourea substituent at C-3' position. Alkaline degradation of these derivatives produced, through corresponding isocyanates cyclic 3'-N,4'-carbonylderivatives. In these anthracycline derivatives with sugar cycles conjugated with oxazoline-2-ones the predominant conformations of sugar ring has changed from 1C4 to 4C1, 2,5B, or B0,3 (shown by 1H NMR spectroscopy). It was demonstrated, both in vitro and in vivo, that introduction of methylurea or cytotoxic methylnitrosourea moieties does not potentiate antimicrobial, cytotoxic or antitumour properties of these compounds.