Pharmacological and physicochemical properties of a new anthracycline with potent antileukemic activity.
The antiproliferative effect of F860191, a new anthracycline with high antitumor activity in L1210 leukemia-inoculated mice, was investigated in vitro on different leukemia cell lines. Comparison of the IC50 value of F860191 with that of daunorubicin and doxorubicin disclosed a superior activity for this drug against the three leukemia cell lines tested. Studies on the mechanism of the antiproliferative activity showed that F860191 induced a G2 + M arrest in the cycle of treated cells. Physicochemical properties of this drug suggested that the high cytotoxic effect of F860191 could be related to its capacity to induce free radicals and to generate DNA breaks through its interaction with topoisomerase II.
Nafziger
J
J
Laboratoire d'Hématologie, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Auclair
C
C
Florent
J C
JC
Guillosson
J J
JJ
Monneret
C
C
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000378:metabolism; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D010084:Oxidation-Reduction
D000903:Antibiotics, Antineoplastic; C063104:moflomycin; D004250:DNA Topoisomerases, Type II; D003630:Daunorubicin