Comparison of antitumor properties of nitracrine and amsacrine analogs.
For seven new methoxy and/or nitro derivatives of acridine antitumor drugs, nitracrine and amsacrine, biological activity in a few in vitro tests, as well as activity against experimental murine tumors Sarcoma-180 and Leukemia L1210 were investigated. Acute toxicity on mice (LD50) was also determined. High activity in vitro and specific activity against Sa-180 were found to be characteristic features of nitracrine, whereas amsacrine was characterized by high antileukemic activity. Methoxylation of position 2 of the acridine ring in both drugs suppressed their characteristic activity. Besides, substitution of the aminoalkyl side chain in nitracrine by methanesulfon-m-anisidine group suppressed its high antitumor activity, and the presence of a nitro group in position 1 of amsacrine suppressed its antileukemic activity. Comparison of biological properties of nitracrine, amsacrine and their analogs indicated differences in some steps of their mode of action.
Mazerska
Z
Z
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Chołody
M
M
Lukowicz
J
J
Wysocka-Skrzela
B
B
Ledóchowski
A
A
D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009564:Nitracrine / Q000494:pharmacology* / Q000633:toxicity; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D012510:Sarcoma 180 / Q000188:drug therapy
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine; D009564:Nitracrine; D010088:Oxidoreductases