5-Ene-4-thiazolidinones induce apoptosis in mammalian leukemia cells

  • Eur J Med Chem. 2016 Jul 19:117:33-46. doi: 10.1016/j.ejmech.2016.03.089.
Julia Senkiv  1 ,  Nataliya Finiuk  1 ,  Danylo Kaminskyy  2 ,  Dmytro Havrylyuk  2 ,  Magdalena Wojtyra  2 ,  Iryna Kril  2 ,  Andrzej Gzella  3 ,  Rostyslav Stoika  1 ,  Roman Lesyk  4
Affiliations
  • 1. Institute of Cell Biology of National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., Lviv 79005, Ukraine.
  • 2. Danylo Halytsky Lviv National Medical University, 69 Pekarska Str., Lviv 79010, Ukraine.
  • 3. Poznan University of Medical Sciences, 6 Grunwaldzka Str., Poznan 60780, Poland.
  • 4. Danylo Halytsky Lviv National Medical University, 69 Pekarska Str., Lviv 79010, Ukraine. Electronic address: [email protected].
PMID: 27089210 DOI: 10.1016/j.ejmech.2016.03.089
Abstract

The article presents the synthesis of 5-ene-4-thiazolidinone derivatives with pyrazole core linked by enamine group. The structure and purity of compounds were confirmed by analytical and spectral data including X-ray analysis. Target compounds were screened for their Anticancer activity and selective antileukemic action was confirmed. 5-[5-(2-Hydroxyphenyl)-3-phenyl-4,5-dihydropyrazol-1-ylmethylene]-3-(3-acetoxyphenyl)-2-thioxothiazolidin-4-one (compound 1) was selected as most active agent against HL-60 and HL-60/ADR cell lines; IC50 = 118 nM/HL-60 with low toxicity towards pseudonormal cells. The mitochondria-depended Apoptosis was identified as the main mode of 1 action. Moreover compound's effect induces G0/G1 arrest of the treated cells and causes inhibition of cell division and is related with activation of ROS production.

Keywords
5-Ene-4-thiazolidinones; Anticancer activity; Apoptosis; Leukemia; ROS.