Synthesis, Characterization, and Anticancer Activity of New N,N′-Diarylthiourea Derivative against Breast Cancer Cells

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Abstract

The goal of the current study was to prepare two new homologous series of N,N′-diarylurea and N,N′-diarylthiourea derivatives to investigate the therapeutic effects of these derivatives on the methodologies of inhibition directed on human MCF-7 cancer cells. The molecular structures of the prepared derivatives were successfully revealed through elemental analyses, 1H-NMR, 13C-NMR and FT-IR spectroscopy. The cytotoxic results showed that Diarylthiourea (compound 4) was the most effective in suppressing MCF-7 cell growth when compared to all other prepared derivatives, with the most effective IC50 value (338.33 ± 1.52 µM) after an incubation period of 24 h and no cytotoxic effects on normal human lung cells (wi38 cells). Using the annexin V/PI and comet tests, respectively, treated MCF-7 cells with this IC50 value of the Diarylthiourea 4 compound displayed a considerable increase in early and late apoptotic cells, as well as an intense comet nucleus in comparison to control cells. An arrest of the cell cycle in the S phase was observed via flow cytometry in MCF-7 cells treated with the Diarylthiourea 4 compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound 4 compared to control cells, suggesting that DNA damage induced by compound 4 may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea 4 compound inhibited the proliferation of MCF-7 cancer cells by arresting the S cell cycle and caspase-3 activation via an intrinsic apoptotic route. These results, however, need to be verified through in vivo studies utilizing an animal model.

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El-Atawy, M. A., Alsubaie, M. S., Alazmi, M. L., Hamed, E. A., Hanna, D. H., Ahmed, H. A., & Omar, A. Z. (2023). Synthesis, Characterization, and Anticancer Activity of New N,N′-Diarylthiourea Derivative against Breast Cancer Cells. Molecules, 28(17). https://doi.org/10.3390/molecules28176420

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