Anticancer effects of the Novel Pyrazolyl-Urea GeGe-3

Williams, Ashleigh; Cooper, Emma; Clark, Bethany; Perry, Laura; Ponassi, Marco; Iervasi, Erika; Brullo, Chiara; Greenhough, Alexander; Ladomery, Michael

Abstract

In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2+-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 μM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action.

Citation

Williams, A., Cooper, E., Clark, B., Perry, L., Ponassi, M., Iervasi, E., …Ladomery, M. (2024). Anticancer effects of the Novel Pyrazolyl-Urea GeGe-3. International Journal of Molecular Sciences, 25(10), Article 5380. https://doi.org/10.3390/ijms25105380

• Journal Article Type: Article
• Acceptance Date: May 10, 2024
• Online Publication Date: May 15, 2024
• Publication Date: May 15, 2024
• Deposit Date: May 15, 2024
• Publicly Available Date: May 15, 2024
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 10
• Article Number: 5380
• DOI: https://doi.org/10.3390/ijms25105380
• Keywords: pyrazole; novel anticancer drugs; cell proliferation; cell migration
• Public URL: https://uwe-repository.worktribe.com/output/11989250
• Additional Information: The article is part of a Special Issue entitled "ynthesis and Biological Evaluation of Pyrazole Derivatives"