Influence of the structure of new anthracycline antibiotics on their biological properties.
In the search for new derivatives of anthracycline antibiotics with advantageous biological properties, particularly with lower toxicity and/or higher activity, a series of new analogs of antibiotics applied in therapy such as daunorubicin, doxorubicin, as well as epidoxorubicin and, for comparison, analogs of epidaunorubicin, have been synthesized. Our results show that the new derivatives have antiproliferative activities similar to or higher than the parent antibiotics. The toxicities of these analogs were significantly lower, with LD50 values from 1.8- to 18.4-fold higher than the referential drugs. Cardiotoxicity determinations, using male mice treated with a single dose of 75% of the LD50 values of all tested compounds, indicated that the cardiotoxicity of the new analogs is significantly lower than that of the parent drugs.
Wasowska
Malgorzata
M
Institute of Biotechnology and Antibiotics, 5 Staroscinska Str., 02-516 Warsaw, Poland. wasowskam@iba.waw.pl
Oszczapowicz
Irena
I
Wietrzyk
Joanna
J
Opolski
Adam
A
Madej
Janusz
J
Dzimira
Stanislaw
S
Oszczapowicz
Janusz
J
D000818:Animals; D018943:Anthracyclines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004317:Doxorubicin / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000031:analogs & derivatives; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; C046084:3'-epidaunorubicin; D004317:Doxorubicin; D003630:Daunorubicin