{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:29:27Z","timestamp":1782984567827,"version":"3.54.5"},"reference-count":97,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSPD2024R1049"],"award-info":[{"award-number":["RSPD2024R1049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Five phenolic Schiff bases (7\u201311) incorporating a fragment of methanesulfonamide were synthesized and evaluated for their efficacy as antitumor agents. Compounds 7 and 8 demonstrated the most potent antitumor action, with a positive cytotoxic effect (PCE) of 54\/59 and 59\/59 and a mean growth percentage (MG%) of 67.3% and 19.5%, respectively, compared with imatinib (PCE = 20\/59 and MG% = 92.6%). The PCE values for derivatives 9\u201311 were 3\/59, 4\/59, and 4\/59, respectively, indicating poor antitumor effect. Compound 8 exhibited the most significant efficacy, suppressing cell proliferation by an average of 50% at a dosage of 0.501 \u00b5M, in comparison with the reference drugs sorafenib (2.33 \u00b5M), gefitinib (2.10 \u00b5M), erlotinib (7.68 \u00b5M), and celecoxib (17.5 \u00b5M). Compounds 7 and 8 had substantial inhibitory effects on the human epidermal growth factor receptor 2 (HER2), with IC50 values of 0.183 \u03bcM and 0.464 \u03bcM, respectively. Furthermore, they exhibited significant inhibition of the epidermal growth factor receptor (EGFR), with IC50 values of 0.752 \u03bcM and 0.166 \u03bcM, respectively. Compound 8 exhibited the highest COX-2 inhibition (IC50 = 12.76 \u03bcM). We performed molecular docking dynamic experiments to examine the precise interaction and structural prerequisites for the anticancer activity of derivatives 7 and 8 by targeting EGFR and HER2.<\/jats:p>","DOI":"10.3390\/ijms252413621","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T10:54:20Z","timestamp":1734605660000},"page":"13621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antitumor Activity and Multi-Target Mechanism of Phenolic Schiff Bases Bearing Methanesulfonamide Fragments: Cell Cycle Analysis and a Molecular Modeling Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-9337","authenticated-orcid":false,"given":"Alaa A.-M.","family":"Abdel-Aziz","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel S.","family":"El-Azab","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-6242","authenticated-orcid":false,"given":"Simone","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rezk R.","family":"Ayyad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hilla, Babylon 6202, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim A.","family":"Al-Suwaidan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Hefnawy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"C A Cancer J. 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