Fares, Mohamed and Alsherbiny, Muhammad and Elkelesh, Islam A. and Said, Mohamed A. and Maklad, Raed M. and Lewis, William and Li, Chun Guang and Eldehna, Wagdy M. and Groundwater, Paul W. and Gale, Philip A. and Keller, Paul A. (2025) Investigating the multi-mechanistic anticancer effects of 4-bisarylurea thiouracil derivatives in breast cancer cells. Bioorganic Chemistry, 162. p. 108581. ISSN 00452068
Full text not available from this repository.Abstract
The study reports the synthesis of a series of 4-bisarylureathiouracil derivatives (6a-e) for potential use in breast cancer treatment. In vitro cytotoxicity was assessed in MCF-7 and MDA-MB-231 human breast cancer cell lines, revealing significant anti-cancer activity. Compound 6e exhibited the highest cytotoxicity, with IC(50) values of 7.94 muM for MCF-7 and 6.67 muM for MDA-MB-231, although it was also the most toxic to RAW 264.7 macrophage cells. In contrast, compound 6c demonstrated strong efficacy against both cancer cell lines (IC(50) = 9.23 +/- 0.6 muM for MCF-7 and 7.72 +/- 0.6 muM for MDA-MB-231) while maintaining selectivity (SI values >10.8 and > 12.9, respectively). Flow cytometry and caspase-3 assays indicated that compounds 6a-c induced apoptosis in MCF-7 cells. In anti-inflammatory assays, compounds 6a and 6d showed significant effects, while 6c demonstrated the weakest, suggesting its cytotoxicity is not linked to anti-inflammatory properties. Compound 6c was prioritised for further investigation because of its preferential targeting of cancer cells. Proteomic analysis of 6c-treated cells revealed significant dysregulation of apoptosis, angiogenesis and VEGF signalling, Rho signal transduction, and pi3k-akt signalling pathways. These findings highlighted the potential of compounds 6a-e as effective anticancer agents, warranting further investigation and optimization for therapeutic applications.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 31 Oct 2025 04:35 |
| Last Modified: | 31 Oct 2025 04:35 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1709 |
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