2. Academic Validation
  3. Chlorine containing tetrahydropyrimidines: Synthesis, characterization, anticancer activity and mechanism of action

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

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: nenad.jankovic@uni.kg.ac.rs.
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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