2. Academic Validation
  3. Bis(4-hydroxy-2H-chromen-2-one): synthesis and effects on leukemic cell lines proliferation and NF-κB regulation

Bis(4-hydroxy-2H-chromen-2-one): synthesis and effects on leukemic cell lines proliferation and NF-κB regulation

  • Bioorg Med Chem. 2014 Jun 1;22(11):3008-15. doi: 10.1016/j.bmc.2014.03.046.
Oualid Talhi 1,  Michael Schnekenburger 2,  Jana Panning 3,  Diana G C Pinto 1,  José A Fernandes 4,  Filipe A Almeida Paz 4,  Claus Jacob 5,  Marc Diederich 6,  Artur M S Silva 7
Affiliations

Affiliations

  • 1 QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
  • 2 Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg.
  • 3 Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg; School of Pharmacy, Building B 2.1., Room 1.13, University of Saarland, Campus, 66123 Saarbrucken, Germany.
  • 4 CICECO, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
  • 5 School of Pharmacy, Building B 2.1., Room 1.13, University of Saarland, Campus, 66123 Saarbrucken, Germany.
  • 6 College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: marcdiederich@snu.ac.kr.
  • 7 QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address: artur.silva@ua.pt.
PMID: 24775915 DOI: 10.1016/j.bmc.2014.03.046
Abstract

Synthesis of the bis-4-hydroxycoumarin-type compound, 3,3'-[3-(2-hydroxyphenyl)-3-oxopropane-1,1-diyl]bis(4-hydroxy-2H-chromen-2-one), was performed by two alternative pathways, either involving a basic organocatalyzed 1,4-conjugate addition tandem reaction of 4-hydroxycoumarin on chromone-3-carboxylic acid, or a double condensation of 4-hydroxycoumarin on ω-formyl-2'-hydroxyacetophenone. The anti-proliferative effects of the bis-4-hydroxycoumarin-type compound on human K-562 (chronic myeloid leukaemia) and JURKAT (acute T-cell leukaemia) cell lines using trypan blue staining, as well as its involvement in nuclear factor-kappa B (NF-κB) regulation analyzed by luciferase reporter gene assay, gene expression analysis and western blots were analysed. This compound inhibited TNFα-induced NF-κB activation in K-562 (IC50 17.5 μM) and JURKAT (IC50 19.0 μM) cell lines, after 8h of incubation. Interestingly, it exerted mainly cytostatic effects at low doses on both cell lines tested, whereas it decreased JURKAT cell viability starting at 50 μM from 24h of treatment. Importantly, it did not affect the viability of peripheral blood mononuclear cells (PBMCs) from healthy donors, even at concentrations above 100 μM.

Keywords

2D-NMR; Biscoumarins; Leukaemia cell lines; NF-κB inhibition; X-ray crystallography.

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