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Comparison of antitumor properties of nitracrine and amsacrine analogs.

Abstract
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.
AuthorsZ Mazerska, M Chołody, J Lukowicz, B Wysocka-Skrzela, A Ledóchowski
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 37 Issue 11 Pg. 1276-81 (Nov 1987) ISSN: 0004-4172 [Print] GERMANY, WEST
PMID3326605 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aminoacridines
  • Antineoplastic Agents
  • Amsacrine
  • Nitracrine
  • Oxidoreductases
Topics
  • Aminoacridines (pharmacology)
  • Amsacrine (pharmacology, toxicity)
  • Animals
  • Antineoplastic Agents (pharmacology, toxicity)
  • HeLa Cells
  • Humans
  • Lethal Dose 50
  • Leukemia L1210 (drug therapy)
  • Mice
  • Mice, Inbred Strains
  • Nitracrine (pharmacology, toxicity)
  • Oxidoreductases (antagonists & inhibitors)
  • Saccharomyces cerevisiae (drug effects, genetics)
  • Sarcoma 180 (drug therapy)

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