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.

• 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"