4-Aryl-N-phenylpyrimidin-2-amines targeting EGFR-tyrosine kinase attenuated EGFR-expressing cell lines

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dc.contributor.authorTabtimmai, Lueacha
dc.contributor.authorSupakun, Prapasri
dc.contributor.authorToviwek, Borvornvat
dc.contributor.authorJiwacharoenchai, Nattanan
dc.contributor.authorKiriwan, Duangnapa
dc.contributor.authorAiebchun, Thitinan
dc.contributor.authorGleeson, M. Paul
dc.contributor.authorChoowongkomon, Kiattawee
dc.date.accessioned2026-08-06T10:37:28Z
dc.date.available2026-08-06T10:37:28Z
dc.date.issued2022-08-01
dc.description.abstractTarget therapies have been widely developed to combat various diseases and cancer. Epidermal Growth Factor Receptor is still a currently therapeutic target for solid tumor. Aberration of EGFR activity or expression reflect disease progression and poor prognosis. Recently, several newly synthesized 4-aryl-N-phenylpyrimidin-2-amines with some modifications at R2 selectively elicited cytotoxicity against A549. Therefore, harboring EGFR expression would be reasonable for the assessment. Herein, the 4-aryl-N-phenylpyrimidin-2-amines derivatives; N-(3-{[4-(4-methoxyphenyl) pyrimidin-2-yl]amino}phenyl), 3-{[4-(3-methoxyphenyl) pyrimidin-2-yl] amino}benzene-1-sulfonamide. (13g), methanesulfonamide (13c), 3-[(4-phenylpyrimidin-2-yl)amino] benzene-1-sulfonamide (13f) and 3-(benzene-1-sulfonamide) (5) were selected as promising derivatives for targeted-EGFR analysis. Kinase enzymatic-based assay exhibited IC<inf>50</inf> values of 5.61, 31.92, 73.80 and 0.79 ​nM of each derivative, respectively whilst 41.50 ​nM of Gefitinib. Molecular docking deciphered the mode of binding of each derivative in ATP-binding site greater than gefitinib. Although, (13g) demonstrated the highest binding free energy among the other but not in ATP-binding site as the others does that related to its IC<inf>50</inf> values. (13c), (13f), and (5) therefore were subjected for cell-based analysis. A549 and A431 were used as wtEGFR-expressing cells for cell-based assay. (13c), (13f), and (5) had high toxicity towards in both cells while (5) had much more toxicity on A431. (13c), (13f) and (5) not only induced apoptosis in a dose-dependent manner but reduced clonogenic formation greater than gefitinib. Migration of EGF-stimulated A431 was significantly delayed by the compounds over time but they could not delay EGF-stimulated A549 migration. Taken together, (13c), (13f) and (5) would be a newly synthesized derivative by targeting wtEGFR-expressing cells that attenuated EGFR-driven cancer hallmark leading to targeted therapy development.
dc.identifier.citationEuropean Journal of Medicinal Chemistry Reports, 5, 2022
dc.identifier.doi10.1016/j.ejmcr.2022.100062
dc.identifier.issn27724174
dc.identifier.other2-s2.0-85148443828
dc.identifier.urihttps://dspace.kmitl.ac.th/handle/123456789/13343
dc.sourceEuropean Journal of Medicinal Chemistry Reports
dc.subject4-Aryl-N-Phenylpyrimidin-2-amine compounds
dc.subjectApoptosis
dc.subjectCancer hallmarks
dc.subjectEpidermal growth factor receptor (EGFR)
dc.subjectTyrosine kinase inhibitors (TKIs)
dc.title4-Aryl-N-phenylpyrimidin-2-amines targeting EGFR-tyrosine kinase attenuated EGFR-expressing cell lines
dc.typeArticle

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