{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:22:06Z","timestamp":1791634926931,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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                    The current study devised and synthesized a novel class of pyrazole derivatives based on indole as possible inhibitors of cyclin\u2010dependent kinase\u20102 (CDK\u20102).\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, NOESY, HMQC, and elemental analysis were used to confirm the structural integrity of the synthesized compounds. Promising CDK\u20102 inhibitory activity was observed in biological assays, and numerous compounds exhibited sub\u2010micromolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values. Compound\n                    <jats:bold>5\u2009d<\/jats:bold>\n                    outperformed the reference inhibitor Roscovitine (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.716\u2009\u00b5M) as the most potent inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.536\u2009\u00b5M), followed by compound\n                    <jats:bold>9\u2009g<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.675\u2009\u00b5M). SAR analysis showed that the observed activity was significantly influenced by the electronic nature of the added substituents as well as the orientation of the indole bond, with brominated derivatives exhibiting greater potency. The antiproliferative activity of the most potent compounds against the cancer cell lines HepG2, HCT\u2010116, and MCF\u20107 was further assessed. In addition to having an enhanced selectivity index for normal MCF\u201010A cells (SI\u2009=\u20098.00 vs. 4.96 for Roscovitine), compound\n                    <jats:bold>5\u2009d<\/jats:bold>\n                    had the greatest activity against MCF\u20107 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20096.78\u2009\u00b5M), surpassing Roscovitine (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20098.11\u2009\u00b5M). According to mechanistic investigations, compound\n                    <jats:bold>5\u2009d<\/jats:bold>\n                    significantly reduced the S\u2010phase population, markedly promoted apoptosis, and caused G1 and G2\/M cell\u2010cycle arrest. Additionally, the consistent binding of compound\n                    <jats:bold>5\u2009d<\/jats:bold>\n                    within the ATP\u2010binding pocket of CDK\u20102 was confirmed by molecular docking and molecular dynamics simulations, and attractive drug\u2010like and pharmacokinetic features, similar to those of Roscovitine, were demonstrated by in silico ADMET predictions. All of these results point to compound\n                    <jats:bold>5\u2009d<\/jats:bold>\n                    as a promising lead scaffold for developing potent CDK\u20102\u2010targeted anticancer agents.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70357","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:09:13Z","timestamp":1786378153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting CDK\u20102 With Novel Indole\u2010Pyrazole Hybrids: Discovery of Potent Anticancer Agents Supported by Mechanistic and In Silico Studies"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4017","authenticated-orcid":false,"given":"Wagdy M.","family":"Eldehna","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6913-356X","authenticated-orcid":false,"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\/0000-0003-0434-2369","authenticated-orcid":false,"given":"Mohamed R.","family":"Elnagar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Al\u2010Azhar University Cairo Egypt"},{"name":"Department of Pharmacology, College of Pharmacy The Islamic University Najaf Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser M.","family":"Omar","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics University of Bradford Bradford UK"},{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Assiut University Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5170-2294","authenticated-orcid":false,"given":"Maha\u2010Hamadien","family":"Abdulla","sequence":"additional","affiliation":[{"name":"Colorectal Research Chair, Department of Surgery, College of Medicine King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-7399","authenticated-orcid":false,"given":"Abdulrahman M.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Chemistry, Faculty of Pharmacy Cairo University, Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9334-5187","authenticated-orcid":false,"given":"Abdelrahman R.","family":"Shalabi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Sinai University North Sinai Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diaaeldin M.","family":"Elimam","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-5590","authenticated-orcid":false,"given":"Suliman","family":"Alshamari","sequence":"additional","affiliation":[{"name":"Colorectal Research Chair, Department of Surgery, College of Medicine King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0589-3955","authenticated-orcid":false,"given":"Mohamed","family":"Fares","sequence":"additional","affiliation":[{"name":"Sydney Pharmacy School The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-5716","authenticated-orcid":false,"given":"Haytham O.","family":"Tawfik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Tanta University Tanta Egypt"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Alsalam University Tanta 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