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Design, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives as novel anti-cancer, dual EGFR WT/COX-2 inhibitors with docking studies

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dc.contributor.authorReda, Nada
dc.contributor.authorElshewy, Ahmed
dc.contributor.authorEL-Askary, Hesham I.
dc.contributor.authorMohamed, Khaled O.
dc.contributor.authorHelwa, Amira A.
dc.date.accessioned2024-03-03T12:42:31Z
dc.date.available2024-03-03T12:42:31Z
dc.date.issued2023-11-02
dc.description.abstractA novel series of pyrimidine-5-carbonitrile derivatives was designed, synthesized, then evaluated for their cytotoxic activity as novel anti-cancer with dual EGFRWT/COX-2 inhibitors. Two compounds 4e and 4f disclosed the highest activity against all NCI60 panel cell lines. They were most potent against Colo 205 (IC50 = 1.66, and 1.83 μM), Sequentially. The most potent two compounds disturbed cell cycle of Colo-205 cells by blocking the G1 phase, coupled with increased annexin-Vstained cells which indicated the increasing in percentage of apoptosis. In addition, 4e and 4f increase the concentration of caspase-3 by 10, and 8-fold compared to control, respectively. Moreover, the two candidate compounds were screened for cytotoxicity on normal epithelial colon cells; fortunately, they were found to be safe. Molecular docking study displayed that these compounds bound to the active site as EGFRWT/COX-2 inhibitors. Furthermore, 3D pharmacophore mapping disclosed many shared features between the most potent candidates 4e and 4f and the standard EGFRWT/COX-2 inhibitors; erlotinib, and celecoxib, respectively. Finally, the physicochemical parameter was calculated for the most potent novel anticancer candidates and the SwissAdme parameter showed that the newly synthesized compounds have good drug-likeness properties.
dc.identifier.citationDi Reda, N., Elshewy, A., El‐Askary, H. I., Mohamed, K. O., & Helwa, A. A. (2023, January 1). Design, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives as novel anti-cancer, dual EGFRWT/COX-2 inhibitors with docking studies. RSC Advances. https://doi.org/10.1039/d3ra06088h
dc.identifier.doi10.1039/d3ra06088h
dc.identifier.issn2046-2069
dc.identifier.pagesPP. 32296-32320
dc.identifier.urihttps://research.gu.edu.eg/handle/123456789/431
dc.language.isoen
dc.publisherRoyal Society of Chemistry
dc.relation.ispartofRSC Advances
dc.source.urihttps://pubs.rsc.org/en/content/articlehtml/2023/ra/d3ra06088h
dc.subjectMolecular
dc.subjectPharmacophore
dc.subjectPhysicochemical
dc.titleDesign, synthesis, and biological evaluation of new pyrimidine-5-carbonitrile derivatives as novel anti-cancer, dual EGFR WT/COX-2 inhibitors with docking studies
dc.typeArticle
dspace.entity.typePublication
oaire.citation.issue46
oaire.citation.volume13
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