{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:08Z","timestamp":1790776868604,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008967","name":"Philipps-Universit\u00e4t Marburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008967","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005712","name":"University of Jordan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005712","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Poly(ADP\u2010ribose) polymerase\u20101 (PARP\u20101) plays a central role in the repair of DNA single\u2010strand breaks and represents an established therapeutic target in cancer treatment. In this study, a series of novel oxadiazole\u2013morpholine hybrid compounds was designed and synthesized using a structure\u2010based drug design approach to target the catalytic domain of PARP\u20101. The synthesized compounds were evaluated for their cytotoxic activity against breast and ovarian cancer cells, PARP\u20101 inhibitory potency, and apoptosis\u2010inducing effects. Among the tested compounds,\n                    <jats:bold>12a<\/jats:bold>\n                    exhibited potent cytotoxic activity against MDA\u2010MB\u2010231 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20091.23\u2009\u03bcM), surpassing the reference drug olaparib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20093.45\u2009\u03bcM). Compound\n                    <jats:bold>12a<\/jats:bold>\n                    also demonstrated strong PARP\u20101 inhibitory activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.034\u2009\u03bcM), comparable to olaparib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.012\u2009\u03bcM). Flow cytometric analyses revealed that compound\n                    <jats:bold>12a<\/jats:bold>\n                    significantly induced apoptotic cell death and altered cell cycle progression. Molecular docking studies suggested plausible binding interactions within the PARP\u20101 catalytic site, supporting the observed biological activity. These findings identify oxadiazole\u2013morpholine hybrids as promising scaffolds for further optimization as PARP\u20101 inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70346","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:46:09Z","timestamp":1783525569000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010Based Design, Synthesis, and Biological Evaluation of Oxadiazole\u2013Morpholine Hybrids as Potent PARP\u20101 Inhibitors Inducing Apoptosis in Breast Cancer Cells"],"prefix":"10.1002","volume":"87","author":[{"given":"Nader R.","family":"Albujuq","sequence":"first","affiliation":[{"name":"Department of Chemistry, School of Science The University of Jordan Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0597-482X","authenticated-orcid":false,"given":"Khaled M.","family":"Darwish","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Department, Faculty of Pharmacy Suez Canal University Ismailia Egypt"},{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Galala University New Galala Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-8281","authenticated-orcid":false,"given":"Sherif Ashraf","family":"Fahmy","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics Marburg University Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9344-0587","authenticated-orcid":false,"given":"Buthaina","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy Al\u2010Zaytoonah University of Jordan Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada G.","family":"Kayed","sequence":"additional","affiliation":[{"name":"Faculty of science Zarqa University Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa A.","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Islamic University of Madinah Madinah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-6390","authenticated-orcid":false,"given":"Mohamed S.","family":"Nafie","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences University of Sharjah Sharjah United Arab Emirates"},{"name":"Bioinformatics and Functional Genomics Research Group, Research, Institute of Sciences and Engineering (RISE) University of Sharjah Sharjah United Arab Emirates"},{"name":"Chemistry Department Faculty of Science, Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557521666210226145837"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105510"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.5958\/0974-360X.2015.00100.6"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2026.109859"},{"issue":"407","key":"e_1_2_7_6_1","first-page":"421","article-title":"Review of the Treatment of Non\u2010Small Cell Lung Cancer With Gefitinib","volume":"6","author":"Araki T.","year":"2012","journal-title":"Clinical Medicine Insights: Oncology"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71123-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-022-11969-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14101269"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2013248"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-010-9455-6"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0345-6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2021.1931181"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10050389"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105770"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100012m"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209608"},{"key":"e_1_2_7_21_1","first-page":"43","volume-title":"Seminars in Immunopathology","author":"Funingana I.\u2010G.","year":"2023"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23123361"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-018-0582-1"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-0138"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.12.003"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-1026-z"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0159341"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03227-6"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2009.034.08.1400202"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01772"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2023.08.001"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0302997"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.2142\/biophysico.16.0_59"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03234-8"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2011.07.006"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13659-017-0143-9"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201803159"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520619666190417153350"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.06.006"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA05966B"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules170910192"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-822312-3.00012-6"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2014_417"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121979119"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.01.019"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo010625v"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2010.491822"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.334516.119"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2019.02.031"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050438"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229891"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.03.038"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0716-2"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.04.089"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557518666181015152433"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(95)00072-I"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2147"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-025-00385-1"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.07.054"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102111"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-026-01673-8"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103730"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.113323"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2024.117762"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c06531"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2023.09.005"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.106"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.979873"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1137151"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70346","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70346","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:34:57Z","timestamp":1790775297000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":69,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ddr.70346"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70346","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"2026-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70346"}}