2. Academic Validation
  3. Highly selective anthraquinone-chalcone hybrids as potential antileukemia agents

Highly selective anthraquinone-chalcone hybrids as potential antileukemia agents

  • Bioorg Med Chem Lett. 2018 Aug 15;28(15):2593-2598. doi: 10.1016/j.bmcl.2018.06.048.
Tatjana Stanojković 1,  Violeta Marković 2,  Ivana Z Matić 1,  Milan P Mladenović 2,  Nina Petrović 3,  Ana Krivokuća 1,  Miloš Petković 4,  Milan D Joksović 5
Affiliations

Affiliations

  • 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, University of Belgrade, 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. Electronic address: mjoksovic@kg.ac.rs.
PMID: 29970309 DOI: 10.1016/j.bmcl.2018.06.048
Abstract

A series of 23 novel anthraquinone-chalcone hybrids containing amide function was synthesized and structurally characterized. Sixteen compounds exerted strong cytotoxic activities against K562, Jurkat and HL-60 leukemia cell lines and significantly lower cytotoxic effects against normal MRC-5 cells, indicating very high selectivity in their Anticancer action. The compounds 6g, 6u and 6v activate Apoptosis in K562 cells through the extrinsic and intrinsic apoptotic pathway. The compound 6e triggered Apoptosis in K562 cells only through the extrinsic apoptotic pathway. Treatment of K562 cells with each of these four compounds caused decrease in the expression levels of MMP2, MMP9, and VEGF, suggesting their anti-invasive, antimetastatic and antiangiogenic properties. The compounds 6g and 6v downregulated expression levels of miR-155 in K562 cells, while compounds 6e and 6u upregulated miR-155 levels in treated cells, in comparison with control cells. The structure-based 3-D QSAR models for 6f, 6e, 6i and 6l describe pro-apoptotic activity against Caspase-3.

Keywords

3-D QSAR; Anthraquinone-chalcone; Gene expression; Leukemia; miR-155.

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