Published June 8, 2018 | Version v.1.0
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Highly selective anthraquinone-chalcone hybrids as potential antileukemia agents

  • 1. Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
  • 2. Faculty of Science, Department of Chemistry, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia
  • 3. Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia; Laboratory for Radiobiology and Molecular Genetics, "Vinča" Institute of Nuclear Sciences, 11000 Belgrade, Serbia
  • 4. Faculty of Pharmacy, Department of Organic Chemistry, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
  • 5. Faculty of Science, Department of Chemistry, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia

Description

A series of 23 novel anthraquinone-chalcone hybrids containing amide function was synthesized and structurallycharacterized. Sixteen compounds exerted strong cytotoxic activities against K562, Jurkat and HL-60 leukemiacell lines and significantly lower cytotoxic effects against normal MRC-5 cells,indicating very high selectivity intheir anticancer action. The compounds 6g, 6uand 6vactivate apoptosis in K562 cells through the extrinsic andintrinsic apoptotic pathway. The compound 6etriggered apoptosis in K562 cells only through the extrinsicapoptotic pathway. Treatment of K562 cells with each of these four compounds caused decrease in the expressionlevels of MMP2, MMP9, and VEGF, suggesting their anti-invasive, antimetastatic and antiangiogenicproperties. The compounds 6gand 6vdownregulated expression levels of miR-155 in K562 cells, while compounds6eand 6uupregulated miR-155 levels in treated cells, in comparison with control cells.The structure-based3-D QSAR models for 6f, 6e, 6iand 6ldescribe pro-apoptotic activity against caspase-3

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BMCL Hihly selective anthraquinone-chalcone hybrids as potential antileukemia agents. 2018_VMarkovic.pdf

Additional details

Related works

Is identical to
10.1016/j.bmcl.2018.06.048 (DOI)
Is part of
0960-894X/ (Handle)

Funding

Ministry of Education, Science and Technological Development
Synthesis, modeling, physicochemical and biological properties of organic compounds and related metal complexes 172016
Ministry of Education, Science and Technological Development
Biological response modifiers in physiological and pathological conditions 175011