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The greatest potent compounds against the four HepG2, HCT116, MCF\u20107, and A549 cell lines were <jats:bold>8f<\/jats:bold> and <jats:bold>8g<\/jats:bold> with IC<jats:sub>50<\/jats:sub>\u2009=\u20094.13, 6.64, 5.74, 6.85\u2009\u00b5M and 4.09, 4.36, 4.22, 7.25\u2009\u00b5M correspondingly. Compound <jats:bold>8g<\/jats:bold> exhibited higher activity than sorafenib against HCT116 and MCF\u20107 but exhibited lower activity against HepG2 and A549. Moreover, compounds <jats:bold>8f<\/jats:bold> and <jats:bold>8g<\/jats:bold> exhibited higher activities than erlotinib on HepG2, HCT116, and MCF\u20107 but demonstrated lower activity on A549. The most potent cytotoxic derivatives <jats:bold>6f<\/jats:bold>, <jats:bold>6g<\/jats:bold>, <jats:bold>8c<\/jats:bold>, <jats:bold>8d, 8e, 8f<\/jats:bold>, and <jats:bold>8g<\/jats:bold> were examined on normal VERO cell lines. Our derivatives have low toxicity on VERO cells with IC<jats:sub>50<\/jats:sub> values ranging from 32.05 to 53.15\u2009\u03bcM. Additionally, all compounds were assessed for dual VEGFR\u20102 and EGFR<jats:sup>T790M<\/jats:sup> inhibition effects. Compounds <jats:bold>8f<\/jats:bold> and <jats:bold>8g<\/jats:bold> were the most potent derivatives inhibited VEGFR\u20102 at IC<jats:sub>50<\/jats:sub> value of 0.88 and 0.90\u2009\u00b5M, correspondingly. As well, derivatives <jats:bold>8f<\/jats:bold> and <jats:bold>8g<\/jats:bold> could inhibit EGFR<jats:sup>T790M<\/jats:sup> demonstrating strongest effects with IC<jats:sub>50<\/jats:sub>\u2009=\u20090.32 and 0.33\u2009\u00b5M sequentially. Additionally, the greatest active derivatives ADMET profile was evaluated in relationship with sorafenib and erlotinib as reference agents. The data attained from docking were greatly related to that achieved from the biological testing.<\/jats:p>","DOI":"10.1002\/ddr.22143","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T08:39:56Z","timestamp":1706344796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["2\u2010Thioxo\u20103,4\u2010dihydropyrimidine and thiourea endowed with sulfonamide moieties as dual EGFR<sup>T790M<\/sup> and VEGFR\u20102 inhibitors: Design, synthesis, docking, and anticancer evaluations"],"prefix":"10.1002","volume":"85","author":[{"given":"Mohamed S. A.","family":"El\u2010Gaby","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science Al\u2010Azhar University Nasr City Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A. 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