Design and synthesis of antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with potential VEGFR-2 inhibitory properties.

Aboshouk, Dalia R., Youssef, M. Adel, Panda, Siva S., Kariuki, Benson M. ORCID: https://orcid.org/0000-0002-8658-3897, Bekheit, Mohamed S., Hamed, Ahmed R., Fayad, Walid, Soliman, Ahmed A. F. and Girgis, Adel S. 2025. Design and synthesis of antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with potential VEGFR-2 inhibitory properties. Scientific Reports 15 (1) , 618. 10.1038/s41598-024-82005-6

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Abstract

Targeted therapy is preferable over other therapeutics due to its limitation of drawbacks and better pharmaceutical outcomes. VEGF and its receptors have been observed to be hyper-activated in many cancer types and are considered promising targets for assigning anticancer agents. The current study is directed towards synthesis of novel antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with VEGFR-2 properties. The targeted agents were obtained through a two-step reaction. Addition of the appropriate 1-(acetylphenyl)-3-phenylurea 9a,b to the corresponding isatin 10a-f in ethanol containing a quantitative amount of Et NH followed by acidic dehydration (AcOH/HCl) afforded the targeted agents 12a-j. Promising antiproliferation properties (MTT assay) were observed for most of the synthesized agents against HCT116 (colon), MCF7 (breast) and PaCa2 (pancreatic) cancer cell lines relative to sunitinib. VEGFR-2 inhibitory properties are consistent with the antiproliferation properties exhibited against the tested cell lines. Compound 12b (R = 4-NHCONHPh, R' = H; % inhibition = 87.2) is the most promising/potent anti-VEGFR-2 agent synthesized with activity close to that of sunitinib (% inhibition = 89.4) at 10 μM. Molecular docking studies (PDB: 3WZE and 3AGD) support the antiproliferation effects against cancer cell lines tested with VEGFR-2 inhibitory properties. The results are consistent with collaboration of the pharmacophores considered (2-oxoindolyl heterocycle and urea) in improving the bio-properties. [Abstract copyright: © 2024. The Author(s).]

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Chemistry
Publisher:	Nature Research
Date of First Compliant Deposit:	17 January 2025
Date of Acceptance:	2 December 2024
Last Modified:	17 Jan 2025 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/175337

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