{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:09:43Z","timestamp":1788966583267,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epidermal growth factor receptor (EGFR) mutations, especially in non\u2013small cell lung cancer (NSCLC), present significant challenges to targeted therapies due to acquired resistance. This study reports the synthesis and evaluation of a series of 4\u2010(2\u2010substituted\u20106\u2010(furan\u20102\u2010yl)pyrimidin\u20104\u2010yl)\u2010substituted phenyl derivatives as potential anticancer agents. The compounds were screened using MTT and brine shrimp lethality assays, identifying\n                    <jats:bold>R2<\/jats:bold>\n                    ,\n                    <jats:bold>R10<\/jats:bold>\n                    , and\n                    <jats:bold>R12<\/jats:bold>\n                    as the most potent against NSCLC cell lines, particularly NCI\u2010H522 and NCI\u2010H1975. Compound\n                    <jats:bold>R12<\/jats:bold>\n                    was most potent and selective against NCI\u2010H522, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 0.95\u00a0\u00b1\u00a00.02\u00a0\u00b5M as compared to standard afatinib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a01.86\u00a0\u00b1\u00a00.22\u00a0\u00b5M). EGFR inhibition assays confirmed\n                    <jats:bold>R12<\/jats:bold>\n                    effectiveness with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 1.62\u00a0\u00b1\u00a00.15\u00a0\u00b5M, 0.49\u00a0\u00b1\u00a00.23\u00a0\u00b5M, and 0.98\u00a0\u00b1\u00a00.02\u00a0\u00b5M against EGFR\n                    <jats:sup>WT<\/jats:sup>\n                    , EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    , and EGFR\n                    <jats:sup>L858R\/T790M\/C797S<\/jats:sup>\n                    , respectively. The compound\n                    <jats:bold>R12<\/jats:bold>\n                    led to the cell cycle arrest in the G2\/M and S phase of NCI\u2010H522 cells with an increase in apoptosis. Molecular docking studies showed\n                    <jats:bold>R12<\/jats:bold>\n                    high binding affinity (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    \u00a0=\u00a0\u221210.2\u00a0kcal\/mol for EGFR\n                    <jats:sup>WT<\/jats:sup>\n                    ;\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    \u00a0=\u00a032.73\u00a0nM) and significant interactions with key amino acids in the active site. Molecular dynamics simulations demonstrated stable protein\u2013ligand interactions with low RMSD (0.17\u20130.27\u00a0nm) and significant eigenvalue (1.706\u00a0\u00d7\u00a010\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). Compound\n                    <jats:bold>R12<\/jats:bold>\n                    also exhibited antioxidant properties against DPPH (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a012.11\u00a0\u00b1\u00a08.96\u00a0\u00b5M) and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a08.89\u00a0\u00b1\u00a01.72\u00a0\u00b5M). Furthermore, DFT analysis and ADMET predictions indicated that\n                    <jats:bold>R12<\/jats:bold>\n                    possesses favorable physiochemical and pharmacokinetic properties, suggesting high bioavailability and minimal toxicity. These findings emphasize\n                    <jats:bold>R12<\/jats:bold>\n                    as a promising lead for further preclinical investigation in overcoming EGFR mutations, including the challenging triple mutation.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202500549","type":"journal-article","created":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T08:07:51Z","timestamp":1745050071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design, Synthesis, and Molecular Profiling of Pyrimidine\u2010Furan Derivatives Targeting EGFR\n                    <sup>WT<\/sup>\n                    , EGFR\n                    <sup>T790M<\/sup>\n                    , and EGFR\n                    <sup>L858R\/T790M\/C797S<\/sup>\n                    in NSCLC: In Vitro and In Silico Evaluation"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2763-5757","authenticated-orcid":false,"given":"Rohit","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Integrated Drug Discovery Centre Acharya &amp; BM Reddy College of Pharmacy  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurubasavaraja Swamy Purawarga","family":"Matada","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Integrated Drug Discovery Centre Acharya &amp; BM Reddy College of Pharmacy  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghanshyam","family":"Teli","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sangam University  Bhilwara India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9460-5304","authenticated-orcid":false,"given":"Md Jawaid","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry National University of Science and Technology  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupinder","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences HNB Garhwal University, Chauras Campus  Srinagar India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2018.1527688"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130206"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200403000-00008"},{"key":"e_1_2_9_5_1","first-page":"48","article-title":"Epidermal Growth Factor Receptor (EGFR) in Lung Cancer: An Overview and Update","volume":"2","author":"Bethune G.","year":"2010","journal-title":"Journal of Thoracic Disease"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0054"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.12.014"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD90040E"},{"key":"e_1_2_9_9_1","first-page":"5","article-title":"Advances on EGFR Mutation for Lung Cancer","volume":"1","author":"Metro G.","year":"2012","journal-title":"Translational Lung Cancer Research"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.107027"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2024.06.004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46284-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573406418666220509100356"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11164-016-2525-8"},{"key":"e_1_2_9_15_1","first-page":"48","article-title":"Medicinal Significance of Furan Derivatives: A Review","volume":"5","author":"Banerjee R.","year":"2015","journal-title":"International Journal of Research in Phytochemistry and Pharmacology"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.04.079"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.03.015"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.12.022"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01434"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1946044"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092552"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.861288"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.04.108"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c01779"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-013-0555-y"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0md00116c"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.22606\/mocr.2016.11001"},{"key":"e_1_2_9_28_1","first-page":"130","article-title":"Novel Oxygen Fused Bicyclic Derivatives and Antioxidant Labelling: Bioactive Chalcone Based Green Synthesis","volume":"13","author":"Bhatt K.","year":"2023","journal-title":"Biointerface Research in Applied Chemistry"},{"key":"e_1_2_9_29_1","unstructured":"N. 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