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

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 <b>4</b>) 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 <b>4</b> 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 <b>4</b> compound, suggesting the onset of apoptosis. Additionally, ELISA research showed that caspase-3 was upregulated in MCF-7 cells treated with compound <b>4</b> compared to control cells, suggesting that DNA damage induced by compound <b>4</b> may initiate an intrinsic apoptotic pathway and activate caspase-3. These results contributed to recognizing that the successfully prepared Diarylthiourea <b>4</b> 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.