resumo
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.
palavras-chave
K562 CELLS; CURCUMIN; CANCER; DIFFERENTIATION; EXPRESSION; APOPTOSIS; DEATH; INHIBITION; ACTIVATION; PATHWAYS
categoria
Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
autores
Talhi, O; Schnekenburger, M; Panning, J; Pinto, DGC; Fernandes, JA; Paz, FAA; Jacob, C; Diederich, M; Silva, AMS
Grupos
agradecimentos
We would like to thank Fundacao para a Ciencia e a Tecnologia (FCT, Portugal), the European Union, QREN, FEDER, COMPETE, for funding the Organic Chemistry Research Unit (QOPNA) (Project PEst-C/QUI/UI0062/2013), Laboratorio Associado Centro de Investigacao em Materiais Ceramicos e Compositos-CICECO (Project PEst-C/CTM/LA0011/2013) and the Portuguese National NMR Network (RNRMN). European Community's Seventh Framework Programme (FP7/2007-20139 under Grant agreement no 215009) is also acknowledged for financial support. We further wish to thank FCT for the post-doctoral Grant SFRH/BD/63736/2009 (to J.A.F.) and for specific funding toward the purchase of the single-crystal X-ray diffractometer. MiS is supported by a 'Waxweiler Grant for cancer prevention research' from the Action Lions 'Vaincre le Cancer'. The work performed at Laboratoire de Biologie Moleculaire et Cellulaire du Cancer was supported by Televie Luxembourg, the << Recherche Cancer et Sang >> foundation, and the << Recherches Scientifiques Luxembourg >> and << Een H erz fir Kriibskrank Kanner >> associations. M. D. is supported by the NRF by the MEST of Korea for Tumor Microenvironment GCRC 2012-0001184 Grant, by the Seoul National University (SNU) Research Grant, by the Research Settlement Fund for the new faculty of SNU and by the Research Institute of Pharmaceutical Sciences.