{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:14:09Z","timestamp":1787062449390,"version":"build-2736575974"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022230","name":"Deanship of Scientific Research, Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2025R116"],"award-info":[{"award-number":["PNURSP2025R116"]}],"id":[{"id":"10.13039\/501100022230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    A novel sulfamoylphenyl-dihydro-thiadiazole derivative (compound\n                    <jats:bold>14<\/jats:bold>\n                    ) has been designed and synthesized as a dual inhibitor targeting EGFR and human carbonic anhydrases (hCA_IX and hCA_XII). Computational studies, including density functional theory (DFT), molecular docking, and molecular dynamics simulations, confirmed its stability, favorable binding interactions, and reactivity profiles. Compound\n                    <jats:bold>14<\/jats:bold>\n                    showed potent inhibition of EGFR (IC\u2085\u2080\u2009=\u200910.12\u2009\u00b1\u20090.29\u2009nM), hCA_IX and hCA_XII (IC\u2085\u2080\u2009=\u200979\u2009\u00b1\u20091.2\u2009nM and 58\u2009\u00b1\u20090.9\u2009nM, respectively). Cytotoxicity assays demonstrated selective activity against cancer cells, with IC\u2085\u2080 values of 16.13 \u00b5M in MDA-MB-231 and 22.57 \u00b5M in MCF-7 cells, compared to 148.32 \u00b5M in non-cancerous Vero cells. Compared to acetazolamide, compound\n                    <jats:bold>14<\/jats:bold>\n                    exhibited improved selectivity for cancer cells. Apoptosis studies revealed significant cell death in MDA-MB-231 cells, with early and late apoptosis rates of 22.50% and 58.27%, respectively, alongside a marked G1-phase cell cycle arrest (49.10% in treated cells vs. 44.98% in controls).\n                    <jats:italic>\n                      <jats:italic>In silico<\/jats:italic>\n                    <\/jats:italic>\n                    toxicological evaluations indicated a favorable safety profile, with low irritancy and acceptable rat oral LD\u2085\u2080 (15.81\u2009mg\/kg) and carcinogenic potency (TD\u2085\u2080\u2009=\u200936.95). Compound\n                    <jats:bold>14<\/jats:bold>\n                    \u2019s potent dual inhibition and selective cytotoxicity make it a promising candidate for further optimization and\n                    <jats:italic>\n                      <jats:italic>in vivo<\/jats:italic>\n                    <\/jats:italic>\n                    studies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0328305","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T17:45:23Z","timestamp":1757007923000},"page":"e0328305","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel sulfamoylphenyl-dihydro-thiadiazole derivative as a dual EGFR and carbonic anhydrase inhibitor for cancer therapy"],"prefix":"10.1371","volume":"20","author":[{"given":"Ibrahim H.","family":"Eissa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-6703","authenticated-orcid":true,"given":"Hazem","family":"Elkady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid E.","family":"Elgammal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem A.","family":"Mahdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal Z.","family":"Husein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma G.","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4870-6758","authenticated-orcid":true,"given":"Asmaa A. 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