This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clement, J. J. Articles by Alder, J. Search for Related Content PubMed PubMed Citation Articles by Clement, J. J. Articles by Alder, J.

Biological Characterization of a Novel Antitumor Quinolone

Abbott Laboratories, Abbott Park, Illinois 60064-3500 [J. J. C., N. B., K. J., D. T. W. C., J. A.], and Arthur D. Little, Inc., Cambridge, Massachusetts 02140-2390 [J. S.]

A-84441, a potent new antitumor quinolone, was active in vitro and in vivo against murine and human tumors. A-84441, a prodrug, was comparable in potency to the parent compound with an IC₅₀ range of 0.03–0.49 µg/ml against a panel of murine and human tumor cell lines. The parent compound bound mammalian DNA in a magnesium-dependent manner and caused inhibition of DNA and RNA synthesis. A-84441 produced a significant increased life span and cures in three lines of i.p. implanted murine tumors. A-84441 was active against seven of nine solid tumors including s.c. murine tumors and human tumor xenografts. The compound appeared to be more active when administered i.v. compared to i.p. injection. Antitumor efficacy was little effected by treatment schedule, although multiple divided dosing was generally more effective than single dose treatment. A-84441 was over 10-fold-more active against murine leukemic cells than against normal murine bone marrow cells. The acute toxicity of A-84441 following single or multiple dosing ranged between 11 and 50 mg/kg dependent on schedule of administration when given by i.v. or i.p. route. The agent had no apparent toxicity or efficacy when administered p.o.

¹ To whom requests for reprints should be addressed, at Abbott Laboratories, Department 4PR, Building AP9A, Abbott Park, IL 60064-3500.

Received 7/ 6/94. Accepted 12/ 8/94.

This article has been cited by other articles:

				V. E. Anderson, R. P. Zaniewski, F. S. Kaczmarek, T. D. Gootz, and N. Osheroff Quinolones Inhibit DNA Religation Mediated by Staphylococcus aureus Topoisomerase IV. CHANGES IN DRUG MECHANISM ACROSS EVOLUTIONARY BOUNDARIES J. Biol. Chem., December 10, 1999; 274(50): 35927 - 35932. [Abstract] [Full Text] [PDF]

				Y. Kwok, Q. Zeng, and L. H. Hurley Structural Insight into a Quinolone-Topoisomerase II-DNA Complex. FURTHER EVIDENCE FOR A 2:2 QUINOBENZOXAZINE-Mg2+ SELF-ASSEMBLY MODEL FORMED IN THE PRESENCE OF TOPOISOMERASE II J. Biol. Chem., June 11, 1999; 274(24): 17226 - 17235. [Abstract] [Full Text] [PDF]