Chlorine containing tetrahydropyrimidines: Synthesis, characterization, anticancer activity and mechanism of action

  • Bioorg Chem. 2024 Oct 23:153:107907. doi: 10.1016/j.bioorg.2024.107907.
Emilija Milović  1 ,  Ivana Z Matić  2 ,  Nina Petrović  3 ,  Ivana Pašić  2 ,  Tatjana Stanojković  2 ,  Miloš R Petrović  4 ,  Goran A Bogdanović  5 ,  Ferda Ari  6 ,  Nenad Janković  7
Affiliations
  • 1. Department of Science, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac 34000, Serbia.
  • 2. Institute for Oncology and Radiology of Serbia, Belgrade 11 000, Serbia.
  • 3. Institute for Oncology and Radiology of Serbia, Belgrade 11 000, Serbia; "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia.
  • 4. Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade 11 000, Serbia.
  • 5. "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia.
  • 6. Department of Biology, Faculty of Science and Art, Bursa Uludag University, Bursa 16059, Turkey.
  • 7. Department of Science, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac 34000, Serbia. Electronic address: [email protected].
PMID: 39490136 DOI: 10.1016/j.bioorg.2024.107907
Abstract

The aim of the presented research was to explore Anticancer potential of eleven newly synthesized tetrahydropyrimidine derivatives. The compounds were synthesized via Biginelli multicomponent one-pot reaction using different derivatives of vanillin, ethyl 4-chloroacetoacetate and (N-methyl)urea. The cytotoxic effects of the compounds were examined on three human malignant cell lines (HeLa, K562, and MCF7), and normal lung fibroblasts MRC-5. The mechanisms of Anticancer activity were examined for two compounds 4a and 4b which showed the strongest and selective cytotoxicity against chronic myelogenous leukaemia K562 cells (IC50 = 1.76 ± 0.09, and 1.66 ± 0.05, respectively). The changes of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor A (VEGFA) were investigated in the K562 cell line, as well as oncomiRNA miR-10b, miR-23a described to have both features, depending on a specific type of malignancy, and miR-34a with mostly described as a tumour suppressor.

Keywords
Cytotoxicity; K562; OncomiRNA; Tetrahydropyrimidines; Tumour suppressor; Vanillin.
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