Published December 29, 2022 | Version v.1
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Synthesis and Cytotoxicity Evaluation of Novel Coumarin–Palladium(II) Complexes against Human Cancer Cell Lines

  • 1. Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia
  • 2. NMR Centre, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
  • 3. NMR Centre, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia; Department of Natural and Health Sciences, Juraj Dobrila University of Pula, Zagrebačka 30, 52100 Pula, Croatia
  • 4. Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
  • 5. Department of Biology and Ecology, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia
  • 6. Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia

Description

Abstract

Two newly synthesized coumarin–palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and 1H-13C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds.

Notes

Funding: This paper is funded through the EIT's HEI Initiative SMART-2M project, supported by EIT RawMaterials, funded by the European Union.

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https://www.mdpi.com/1424-8247/16/1/49 (URL)
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1424-8247 (ISSN)
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https://www.mdpi.com/1424-8247/16/1/49#app1-pharmaceuticals-16-00049 (URL)