Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives
Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Co...
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| Autores principales: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/c7197d877528405aa0fda44bf124f5f6 |
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| Sumario: | Substituted thiourea derivatives possess confirmed cytotoxic activity towards cancer but also normal cells. To develop new selective antitumor agents, a series of 3-(trifluoromethyl)phenylthiourea analogs were synthesized, and their cytotoxicity was evaluated in vitro against the cell line panel. Compounds <b>1</b>–<b>5</b>, <b>8</b>, and <b>9</b> were highly cytotoxic against human colon (SW480, SW620) and prostate (PC3) cancer cells, and leukemia K-562 cell lines (IC<sub>50</sub> ≤ 10 µM), with favorable selectivity over normal HaCaT cells. The derivatives exerted better growth inhibitory profiles towards selected tumor cells than the reference cisplatin. Compounds incorporating 3,4-dichloro- (<b>2</b>) and 4-CF<sub>3</sub>-phenyl (<b>8</b>) substituents displayed the highest activity (IC<sub>50</sub> from 1.5 to 8.9 µM). The mechanisms of cytotoxic action of the most effective thioureas <b>1</b>–<b>3</b>, <b>8</b>, and <b>9</b> were studied, including the trypan blue exclusion test of cell viability, interleukin-6, and apoptosis assessments. Compounds reduced all cancerous cell numbers (especially SW480 and SW620) by 20–93%. Derivatives <b>2</b> and <b>8</b> diminished the viability of SW620 cells by 45–58%. Thioureas <b>1</b>, <b>2</b>, and <b>8</b> exerted strong pro-apoptotic activity. Compound <b>2</b> induced late apoptosis in both colon cancer cell lines (95–99%) and in K-562 cells (73%). All derivatives acted as inhibitors of IL-6 levels in both SW480 and SW620 cells, decreasing its secretion by 23–63%. |
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