Selective cytotoxicity of diazenecarboxamides towards human leukemic cell lines.
In this study, the cytotoxicity of 16 diazenes towards four human leukemic cell lines was tested. Regarding their structure these 16 diazenes belong to three subclasses: diazenecarboxamides (11 compounds), diazenedicarboxamides (4 compounds) and alkyl aminocarbonyldiazenecarboxylate (1 compound). The leukemic cell lines used in this study were NALM-1, JURKAT, HL-60 and K-562. Fifteen out of 16 tested diazenes were cytotoxic towards the leukemic cell lines: 11 with high efficacy (IC(50)<50 microM) at least towards two to three leukemic cell lines, and 4 with medium efficacy (IC(50)>50 microM). Ten out of these 11 diazenes have a common structure and belong to the subclass of diazenecarboxamides. Five diazenes (SB-681, LK-34, UP-39, JK-1197, UP-11) were highly cytotoxic (IC(50) values 3.3-38.9 microM) towards all four leukemic cell lines. The selectivity of the cytotoxicity towards leukemic cells was tested by using resting and Con-A-stimulated peripheral blood mononuclear cells (PBMC) isolated from healthy donors and towards normal mouse fibroblast cell line, 3T3. The diazenes cytotoxic towards leukemic cells, did not affect the viability of the resting PBMC suggesting selectivity of their action. Moreover, eight diazenes did not affect the normal dividing cells (Con-A-stimulated PBMC and fibroblasts). Thus, we present eight diazenes which are selectively cytotoxic towards leukemic cells, not affecting normal cells even when activated to proliferation. These compounds may represent new potential agents for the treatment of leukemia patients.
Ruder Bosković Institute, Division of Molecular Medicine, Bijenicka cesta 54, HR-10002 Zagreb, Croatia. kleiner@irb.hr
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Martin-Kleiner
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Bombek
J
J
Kosmrlj
B
B
Cupić
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T
Cimbora-Zovko
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Jakopec
S
S
Polanc
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M
Osmak
J
J
Gabrilovac
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007094:Imides / Q000737:chemistry / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy*; D015394:Molecular Structure
D000970:Antineoplastic Agents; D007094:Imides