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

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 omega-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-kappa B) regulation analyzed by luciferase reporter gene assay, gene expression analysis and western blots were analysed. This compound inhibited TNF alpha-induced NF-kappa B activation in K-562 (IC50 17.5 mu M) and JURKAT (IC50 19.0 mu M) cell lines, after 8 h 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 mu M from 24 h of treatment. Importantly, it did not affect the viability of peripheral blood mononuclear cells (PBMCs) from healthy donors, even at concentrations above 100 mu M. (C) 2014 Elsevier Ltd. All rights reserved.