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image of Urea and Thiourea Derivatives of Salinomycin as Agents Targeting Malignant Colon Cancer Cells

Abstract

Background

Since it was discovered that a natural polyether ionophore called salinomycin (SAL) selectively inhibits human cancer cells, the scientific world has been paying special attention to this compound. It has been studied for nearly 15 years.

Objective

Thus, a very interesting research direction is the chemical modification of structure, which could give more biologically active agents.

Methods

We evaluated the anticancer activity of (thio)urea analogues class of C20--aminosalinomycin (compound ). The studies covered the generation of reactive oxygen species (ROS), proapoptotic activity, cytotoxic activity, and lipid peroxidation .

Results

Thioureas showed antiproliferative activity against selected human colon cancer cell lines greater than that of chemically unmodified , with a 2~10-fold higher potency towards a metastatic variant of colon cancer cells (SW620). Mechanistically, derivatives showed pro-apoptotic activity in primary colon cancer cells and induced the production of reactive oxygen species (ROS) in these cells. In SW620 cells, derivatives increased lipid peroxidation with a weak effect on apoptosis and low ROS formation with cytotoxic effects followed by cytostatic ones, suggesting different modes of action of the compounds against primary and metastatic colon cancer cells.

Conclusion

The results of this study suggested that urea and thiourea derivatives of provide promising leads for the rational development of new anticancer active agents.

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2024-10-14
2024-12-04

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Urea and Thiourea Derivatives of Salinomycin as Agents Targeting Malignant Colon Cancer Cells
Bentham Science Publishers ; https://doi.org/10.2174/0118715206322603241002064435
/content/journals/acamc/10.2174/0118715206322603241002064435
/content/journals/acamc/10.2174/0118715206322603241002064435
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  • Article Type:     Research Article
Keywords: colorectal cancer ; ROS ; Ionophores ; apoptosis ; lipid peroxidation ; cytotoxicity

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