Cytotoxic action and cell cycle effects of ALGA, a peptidic derivative of the antileukemic drug amsacrine.
4'-(9-acridinylamino) methanesulfon-m-anisidide (amsacrine or AMSA), an antitumor drug which has been tested in clinical trials, is known to bind to DNA by the intercalation of its 9-amino acridine moiety between DNA base pairs. Like AMSA, a peptidic derivative of 4-(9-acridinylamino) aniline, 4-(9-acridinylamino)-N-(lysylglycyl) aniline (ALGA) binds to DNA by intercalation and its affinity for the target was found to be higher than the parent drug. The antitumor effect of AMSA and ALGA has been monitored by drug exposure assays on EMT 6 cells. AMSA showed a slightly higher cytotoxic activity. The cell cycle effects of both drugs were studied using flow cytofluorimetry; an accumulation of cells in the S phase followed by a cycle arrest in the G2 phase, characteristic of intercalating drugs, was observed.
Unité 124 INSERM, Institut de Recherches sur le Cancer de Lille, France.
M
M
Collyn-d'Hooghe
J L
JL
Bernier
J P
JP
Henichart
D000677:Amsacrine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D013053:Spectrophotometry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004151:Dipeptides; D000677:Amsacrine; C054943:4-(9-acridinylamino)-N-(lysylglycyl)aniline; D004247:DNA