BIOLOGICAL CHARACTERIZATION OF A NOVEL ANTITUMOR QUINOLONE

A-84441, a potent new antitumor quinolone, was active in vitro and in vivo against murine and human tumors. A-84441, a prodrug, was comparab le in potency to the parent compound with an IC50 range of 0.03-0.49 m u g/ml against a panel of murine and human tumor cell Lines. The paren t compound bound mammalian DNA in a magnesium-dependent manner and cau sed inhibition of DNA and RNA synthesis. A-84441 produced a significan t increased life span and cures in three lines of i.p. implanted murin e tumors. A-84441 was active against seven of nine solid tumors includ ing s.c. murine tumors and human tumor xenografts. The compound appear ed to be more active when administered i.v. compared to i.p. injection . Antitumor efficacy was little effected by treatment schedule, althou gh multiple divided dosing was generally more effective than single do se treatment. A-84441 was over 10-fold-more active against murine leuk emic cells than against normal murine bone marrow cells. The acute tox icity 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.