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.

Production of organic acids from fermentation of mannitol, fructooligosaccharide and inulin by a cholesterol removing Lactobacillus acidophilus strain

“…Acetate can reduce the concentration of serum fatty acids, which is an important factor in lowering glucose utilization by tissues and inducing insulin resistance. Long‐term dietary supplementation with propionate was shown to decrease blood glucose in rats and humans, while butyrate possessed antineoplastic properties and is mostly used by colonocytes as an energy source (Gillet et al. 1998; Rizkalla et al.…”

Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines

“…Piperizine derivatives were shown to inhibit growth inhibition of human erythroleukemia K5-62 cells and myeloid leukemia HL-60 cells [26] and also shown to inhibit topoisomarase II activity [27]. Wilson et al reported the interaction of DNA with unfused aromatic system containing terminal piperazino substituents [9].…”

Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2- benzoisothiazoles as potent apoptotic agents

“…Whilst chemotherapeutic drugs are known to induce autophagy, cell cycle arrest and cell senescence [4,5], it is imperative that there is induction of apoptosis and permanent removal of neoplastic cells for effective cancer chemotherapy. Recently, benzoisothiazole, Isoxazole and piperazine rings have been shown to exhibit varied biological activities including anticancer properties [6][7][8][9][10][11].…”