Antiproliferative and erythroid differentiation of piperazine and triphenyl derivatives against k-562 human chronic myelogenous leukemia

Anticancer Res. 2013 Aug;33(8):3027-32.

Abstract

Five piperazine derivatives (S)-4-benzyl-1-(4-bromo-3-methylphenyl)-2 methylpiperazine (A), (S)-1-benzyl-3-isobutylpiperazine-2,5-dione (B), (S)-1-benzyl-3 methylpiperazine-2,5-dione (C), (S)-1,3-dibenzylpiperazine-2,5-dione (D), (E)-1-(3-methyl 4-((E)-3-(2-methylpropylidene) piperazin-1-yl) phenyl)-2-(2 methylpropylidene) piperazine (E) and triphenyl derivative ammonium 2-((2,3',3''-trimethyl-[1,1':4',1''-terphenyl]-4 yl)oxy)acetate (F) were tested for inhibition of K-562 cell proliferation and for induction of erythroid differentiation. Among them, two piperazine and one triphenyl derivatives, compounds A, E, and F inhibited the proliferation of the K562 cell lines exhibiting inhibition concentration 50 (IC50) (IC50) of values 30.10±1.6, 4.60±0.4 and 25.70±1.10 μg ml(-1), respectively. If compound A and F were added to suboptimal concentrations of the established anticancer drugs cytosine arabinoside or mithramycin, pronounced synergic effects were observed.

Keywords: Antiproliferative activity; anticancer agents; erythroid differentiation; piperazine derivatives; triphenyl derivatives.

MeSH terms

  • Cell Death / drug effects
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Erythroid Cells / drug effects
  • Erythroid Cells / metabolism
  • Erythroid Cells / pathology
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Piperazine
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Plicamycin / pharmacology
  • Terphenyl Compounds / chemistry
  • Terphenyl Compounds / pharmacology*

Substances

  • Piperazines
  • Terphenyl Compounds
  • Piperazine
  • Plicamycin