{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:56:58Z","timestamp":1785351418983,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A series of 1,3,4\u2010oxadiazole\u2010benzimidazole\/acetamide derivatives (\n                    <jats:bold>7a\u2013r<\/jats:bold>\n                    ) was designed, synthesized, and evaluated for their anticancer activity. NCI\u2010screening results at 10\u2009\u00b5M against the 60 human tumor cell line panel revealed a broad\u2010spectrum of antiproliferative effects of the tested compounds. Compounds\n                    <jats:bold>7b<\/jats:bold>\n                    ,\n                    <jats:bold>7e<\/jats:bold>\n                    ,\n                    <jats:bold>7f<\/jats:bold>\n                    ,\n                    <jats:bold>7g<\/jats:bold>\n                    ,\n                    <jats:bold>7h<\/jats:bold>\n                    ,\n                    <jats:bold>7k<\/jats:bold>\n                    ,\n                    <jats:bold>7l<\/jats:bold>\n                    , and\n                    <jats:bold>7r<\/jats:bold>\n                    were further tested in a five\u2010dose assay, and they exhibited half\u2010maximal growth inhibitory (GI\n                    <jats:sub>50<\/jats:sub>\n                    ) values ranging from 0.90 to 43.50\u2009\u00b5M. Focused studies in MDA\u2010MB\u2010231 triple\u2010negative breast cancer (TNBC) cells demonstrated that compounds\n                    <jats:bold>7b<\/jats:bold>\n                    ,\n                    <jats:bold>7g<\/jats:bold>\n                    ,\n                    <jats:bold>7h<\/jats:bold>\n                    ,\n                    <jats:bold>7k<\/jats:bold>\n                    , and\n                    <jats:bold>7l<\/jats:bold>\n                    possessed potent antiproliferative activity, with half\u2010maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) values between 1.92 and 3.69\u2009\u00b5M. Mechanistic investigations using cell death pathway inhibitors indicated that compounds\n                    <jats:bold>7b<\/jats:bold>\n                    ,\n                    <jats:bold>7k<\/jats:bold>\n                    , and\n                    <jats:bold>7l<\/jats:bold>\n                    did not induce necrosis, apoptosis, or autophagy. Instead, these compounds significantly increased intracellular ferrous iron (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ) and malondialdehyde (MDA) levels and induced lipid peroxidation in MDA\u2010MB\u2010231 cells. In parallel, GPX4 expression was markedly reduced at both the mRNA and protein levels, supporting ferroptosis as the primary mechanism of action. In addition, molecular docking studies and molecular dynamics simulations were performed for derivatives\n                    <jats:bold>7b<\/jats:bold>\n                    ,\n                    <jats:bold>7k<\/jats:bold>\n                    , and\n                    <jats:bold>7l<\/jats:bold>\n                    in order to confirm the mechanistic study. Collectively, these findings suggest that the 1,3,4\u2010oxadiazole\u2013benzimidazole\/acetamide scaffold represents a promising chemotype for developing ferroptosis\u2010inducing therapeutics targeting TNBC.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70229","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:03:47Z","timestamp":1774418627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ferroptosis\u2010Driven Anticancer Activity of 1,3,4\u2010Oxadiazole\u2013Benzimidazole\/Acetamide Hybrids: Design, Synthesis, and Biological Profiling"],"prefix":"10.1002","volume":"359","author":[{"given":"Fatma Fouad","family":"Hagar","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia University  Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4822-6581","authenticated-orcid":false,"given":"Amer Ali","family":"Abd El\u2010Hafeez","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9586-2644","authenticated-orcid":false,"given":"Samar H.","family":"Abbas","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia University  Minia Egypt"},{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia National University  New Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Nahda University  Beni\u2010Suef Egypt"},{"name":"Department of Pharmacognosy, Collage of Pharmacy Almaaqal University  Basrah Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Abdelfattah","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics Texas A&amp;M University Health Science Center  Bryan Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba S.","family":"Abd\u2010Ellah","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia University  Minia Egypt"},{"name":"Medicinal Chemistry Department Monash Institute of Pharmaceutical Sciences  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Abdelhamid","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia University  Minia Egypt"},{"name":"Raabe College of Pharmacy Ohio Northern University  Ada Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abdel\u2010Aziz","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia University  Minia Egypt"},{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Minia National University  New Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-16-7945-2_4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djab122"},{"issue":"2","key":"e_1_2_8_6_1","first-page":"12","article-title":"DNA Interaction of Drug Molecules for Cancer Treatment","volume":"2","author":"Abu\u2010Dief A. 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