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

[Display omitted] •Eleven new tetrahydropirimidines were synthesized via Biginelli reaction.•The anticancer activity was examined on HeLa, K562, MCF7, and MRC-5 cell lines.•4a and 4b showed IC50 = 1.76, and 1.66 µM, respectively against K562 cells.•The presence of N-methyl group is crucial for anticancer activity.•4a and 4b have significant effects on gene and miRNA signatures in K562 cells. 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.