title: Piperazine derivatives of butyric acid as differentiating agents in human leukemic cells.
abstract: Butyric acid is a potent antineoplastic agent with a well-documented differentiation activity on a wide variety of tumor cells. However, its clinical development is strongly limited by its very short metabolic half-life. In this study we report on the in vitro effects of new original piperazine derivatives of butyric acid on the induction of differentiation and the growth inhibition of human erythroleukemia K562 cells and myeloid leukemia HL60 cells. 1-(2-hydroxyethyl) 4-(1-oxobutyl)-piperazine (HEPB) and [1-(2-hydroxyethyl) 4-(1-oxobutyl)-piperazine] butyrate (HEPDB) were efficient in acting on the differentiation and proliferation of both cell lines, whereas 1-phenyl 4-(1-oxobutyl)-piperazine (PPB) and 1-(3,4-methylene dioxybenzyl) 4-(1-oxobutyl)-piperazine (POB) acted only on proliferation rates. Such derivatives did not induce significant toxicity in mice. These preliminary results should enable, by the development of new series of piperazine derivatives, a better understanding of the mechanisms of action of butyric acid and its analogues on the coupling of growth and differentiation of neoplastic cells.
authors.affiliation: Laboratoire de Biochimie et Biologie Moléculaire, Faculté de Pharmacie, IFR 53, Centre des Biomolécules, Reims, France.
authors.forename: R
authors.initials: R
authors.lastname: Gillet
authors.forename: P
authors.initials: P
authors.lastname: Jeannesson
authors.forename: H
authors.initials: H
authors.lastname: Sefraoui
authors.forename: M L
authors.initials: ML
authors.lastname: Arnould-Guérin
authors.forename: S
authors.initials: S
authors.lastname: Kirkiacharian
authors.forename: J C
authors.initials: JC
authors.lastname: Jardillier
authors.forename: F
authors.initials: F
authors.lastname: Pieri
mesh_terms: D000818:Animals; D002087:Butyrates / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D002087:Butyrates; D010879:Piperazines