{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:37:51Z","timestamp":1783960671640,"version":"3.55.0"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Humanity is currently facing various diseases with significant mortality rates, particularly those associated with malignancies. Numerous enzymes and proteins have been identified as highly promising targets for the treatment of cancer. The poly(ADP\u2010ribose) polymerases (PARPs) family comprises 17 members which are essential in DNA damage repair, allowing the survival of cancer cells. Unlike other PARP family members, PARP\u20101 and, to a lesser extent, PARP\u20102 show more than 90% activity in response to DNA damage. PARP\u20101 levels were shown to be elevated in various tumor cells, including breast, lung, ovarian, and prostate cancer and melanomas. Accordingly, novel series of phthalimide\u2010tethered isatins (<jats:bold>6a\u2010n<\/jats:bold>, <jats:bold>10a\u2010e<\/jats:bold>, and <jats:bold>11a\u2010e<\/jats:bold>) were synthesized as potential PARP\u20101 inhibitors endowed with anticancer activity. All the synthesized molecules were assessed against PARP\u20101, where compounds <jats:bold>6f<\/jats:bold> and <jats:bold>10d<\/jats:bold> showed nanomolar activities with IC<jats:sub>50<\/jats:sub>\u2009=\u200915.56\u2009\u00b1\u20092.85 and 13.65\u2009\u00b1\u20091.42\u2009nM, respectively. Also, the assessment of the antiproliferative effects of the synthesized isatins was conducted on four cancer cell lines: leukemia (K\u2010562), liver (HepG2), and breast (MCF\u20107 and HCC1937) cancers. Superiorly, compounds <jats:bold>6f<\/jats:bold> and <jats:bold>10d<\/jats:bold> demonstrated submicromolar IC<jats:sub>50<\/jats:sub> values against breast cancer MCF\u20107 (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.92\u2009\u00b1\u20090.18 and 0.67\u2009\u00b1\u20090.12\u2009\u00b5M, respectively) and HCC1937 (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.88\u2009\u00b1\u20090.52 and 0.53\u2009\u00b1\u20090.11\u2009\u00b5M, respectively) cell lines. In addition, compounds <jats:bold>6f<\/jats:bold> and <jats:bold>10d<\/jats:bold> induced arrest in the G2\/M phase of the cell cycle as compared to untreated cells. Finally, in silico studies, including docking and molecular dynamic simulations, were performed to justify the biological results.<\/jats:p>","DOI":"10.1002\/ardp.202300599","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T18:10:30Z","timestamp":1702663830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Phthalimide\u2010tethered isatins as novel poly(ADP\u2010ribose) polymerase inhibitors: Design, synthesis, biological evaluations, and molecular modeling investigations"],"prefix":"10.1002","volume":"357","author":[{"given":"Mahmoud A.","family":"El Hassab","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy King Salman International University (KSIU) Ras Sudr South Sinai Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer Ali Abd","family":"El\u2010Hafeez","sequence":"additional","affiliation":[{"name":"Cancer Biology Department, Pharmacology and Experimental Oncology Unit,\u00a0National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadia","family":"Almahli","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab M.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Scientific Research and Innovation Support Unit, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4017","authenticated-orcid":false,"given":"Wagdy M.","family":"Eldehna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"},{"name":"School of Biotechnology Badr University in Cairo Badr City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaneya S.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Cairo University Cairo Egypt"},{"name":"Pharmaceutical Chemistry Department, School of Pharmacy Badr University in Cairo (BUC) Badr City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar M.","family":"Abou\u2010Seri","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190215121712"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2013.04.007"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes7080051"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00648-7"},{"key":"e_1_2_5_6_1","first-page":"4363","volume":"59","author":"Fischhaber P. 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