{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:25:40Z","timestamp":1791599140951,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100022230","name":"Deanship of Scientific Research, Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R325"],"award-info":[{"award-number":["PNURSP2026R325"]}],"id":[{"id":"10.13039\/501100022230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This work describes the design, synthesis, and anticancer evaluation of a new acridine hybrid (ACNP). ACNP showed cytotoxic effect with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 4.3 and 10\u2009\u03bcg\/mL against MCF\u20107 and MDA\u2010MB 231; respectively, versus CC\n                    <jats:sub>50<\/jats:sub>\n                    value of 439.72\u2009\u03bcg\/mL of normal lung fibroblast cells (WI\u201038 cells) with high selectivity index (SI) of 102.2 and 43.9 for MCF\u20107 and MDA\u2010MB 231 of cancer cells respectively. ACNP showed a cytotoxic synergetic effect when combined with paclitaxel in MDA\u2010MB 231 and MCF\u20107 cell lines. A significant down regulation of PI3K, mTOR and AKT was demonstrated in cells treated with paclitaxel or ACNP as single therapy with minimal expression in cells treated with combination of both. ACNP treated cells recorded an increase in protein expression level of Caspase\u20103, Caspase\u20109 while Ki67 showed a declined expression in MDA\u2010MB 231 and MCF\u20107 cell lines. Molecular docking investigation was performed on PI3K and Caspase\u20103 to predict the possible binding modes of the acridine tricyclic skeleton with the molecular targets. The ADME study revealed that ACNP has high GI absorption and blood brain barrier although oral bioavailability was poor. These results suggested that ACNP maybe a promising candidate for further preclinical development.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70269","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T13:55:50Z","timestamp":1772978150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti\u2010Proliferative and Apoptotic Evaluation of a Novel Synthesized Acridine Hybrid With Anticipated Synergistic Effect to Paclitaxel on Breast Cancer Cells"],"prefix":"10.1111","volume":"107","author":[{"given":"Esraa A.","family":"Aidy","sequence":"first","affiliation":[{"name":"Medical Biochemistry and Molecular Biology, Department of Cancer Biology National Cancer Institute, Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-5040","authenticated-orcid":false,"given":"Elshaymaa I.","family":"Elmongy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Capital University (formerly Helwan University)  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah A. S.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Menoufia University  Shebin El\u2010Kom Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim El Tantawy","family":"El Sayed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Menoufia University  Shebin El\u2010Kom Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan Ali","family":"Henidi","sequence":"additional","affiliation":[{"name":"Research Department, Health Sciences Research Center Princess Nourah Bint Abdulrahman University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad M.","family":"EL\u2010Gendy","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology, Department of Cancer Biology National Cancer Institute, Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin S.","family":"EL\u2010Gendy","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Faculty of Dentistry Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Ibrahim","family":"El\u2010Tantawy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Menoufia University  Shebin El\u2010Kom Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2665-5681","authenticated-orcid":false,"given":"Heba","family":"Effat","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology, Department of Cancer Biology National Cancer Institute, Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05994.x"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13738-019-01849-2"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.701301"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17111487"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2018.1558202"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1879"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9OB00318E"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.44"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020102v"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-018-2776-4"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19910915)68:6<1309::AID-CNCR2820680621>3.0.CO;2-I"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.06.045"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants12112203"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17020188"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310827"},{"key":"e_1_2_13_18_1","volume-title":"Global Cancer Observatory: Cancer Today","author":"Ferlay J.","year":"2020"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.8.2672"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041142"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2015.04.002"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7RA01026E"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/cc9800071"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-019-03576-x"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3987\/COM-15-13210"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202200146"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3791\/64308"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2020.111690"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.15171\/apb.2019.024"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11094-015-1181-4"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2012.04.039"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1993.488"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-0256-5"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25010064"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.04.053"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008656"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.11.044"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00090"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00573"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00104"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.5092"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2421"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096502"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.aihch.2015.04.004"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13017"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02309-9"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/82.13.1107"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317695011"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10020345"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28010193"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.8.2134"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-023-03524-z"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.245"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31374"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70269","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.70269","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T11:54:52Z","timestamp":1775994892000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.70269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/cbdd.70269"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.70269","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2024-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70269"}}