Adriamycin analogues. Preparation and antitumor evaluation of 7-O-(beta-D-glucosaminyl)daunomycinone and 7-O-(beta-D-glucosaminyl)adriamycinone and their N-trifluoroacetyl derivatives.
The title compounds were prepared by Koenigs-Knorr condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-[(trifluoroacetyl)amino]-alpha-D-glucopyranosyl bromide with daunomycinone or a side-chain protected adraimycinone, followed by selective hydrolysis of blocking groups. Despite poor complexation with DNA and weak growth-inhibitory properties in vitro, the glucosaminyl analogues of the antitumor antibiotics daunorubicin and adriamycin, at their optimal (highest nontoxic) doses, exhibited antileukemic activity equivalent to that of adriamycin against a usually drug-refractory mouse leukemia model system (L1210) in vivo. These findings, together with other data from these laboratories, continue to support the hypothesis that the mechanism of action of adriamycin and related agents cannot be due exclusively to DNA binding, as has earlier been believed.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D004247:DNA