期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 22, 期 11, 页码 3008-3015出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.03.046
关键词
Biscoumarins; 2D-NMR; X-ray crystallography; Leukaemia cell lines; NF-kappa B inhibition
资金
- Fundacao para a Ciencia e a Tecnologia (FCT, Portugal)
- European Union
- QREN
- FEDER
- COMPETE
- Organic Chemistry Research Unit (QOPNA) [PEst-C/QUI/UI0062/2013]
- Laboratorio Associado Centro de Investigacao em Materiais Ceramicos e Compositos-CICECO [PEst-C/CTM/LA0011/2013]
- Portuguese National NMR Network (RNRMN)
- European Community [215009]
- GCRC [2012-0001184]
- Seoul National University (SNU) Research Grant
- Research Settlement Fund for the new faculty of SNU
- Research Institute of Pharmaceutical Sciences
- [SFRH/BD/63736/2009]
- National Research Foundation of Korea [2011-0030001] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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