{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:16:17Z","timestamp":1782756977944,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer is among the leading causes of death in the world today. Several strategies were used to control cancer including chemotherapy, radiotherapy and targeted therapy. Among the problems related to antiproliferative chemotherapy against cancer is the medication resistance which require continuous generation of new agents. These new potential agents could be extracted from natural sources or prepared synthetically. This research represents the preparation of new heterocycles incorporating an indenopyridazine nucleus as potential antiproliferative agents. The synthetic strategy was initiated by the treatment of ninhydrin with cyanoacetohydrazide resulting in the formation of the key intermediate indeno[2,1\u2010\n                    <jats:italic>c<\/jats:italic>\n                    ]pyridazine scaffold\n                    <jats:bold>4<\/jats:bold>\n                    , which undergoes condensation with various nitrogenous nucleophilic reagents (namely: phenyl hydrazine, substituted benzohydrazide, and thiosemicarbazide). Cyclization of thiosemicarbazone derivative\n                    <jats:bold>8<\/jats:bold>\n                    with ethyl bromoacetate furnished the target compound thiazolin\u20104\u2010one derivative\n                    <jats:bold>9<\/jats:bold>\n                    , which was condensed with three 5\u2010aryl\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyrazole\u20104\u2010carbaldehydes to furnish the corresponding 5\u2010arylidene\u2010thiazolin\u20104\u2010one derivatives\n                    <jats:bold>11a\u2010c<\/jats:bold>\n                    . In addition, thiosemicarbazone derivative\n                    <jats:bold>8<\/jats:bold>\n                    undergoes reactions with \u03b1\u2010chloroesters\n                    <jats:bold>12<\/jats:bold>\n                    or \u03b1\u2010chloroketones\n                    <jats:bold>14<\/jats:bold>\n                    to yield the indenopyridazine\u2010thiazole hybrids\n                    <jats:bold>13<\/jats:bold>\n                    and\n                    <jats:bold>15<\/jats:bold>\n                    , respectively. The cytotoxic activity of the targeted indeno[2,1\u2010\n                    <jats:italic>c<\/jats:italic>\n                    ]pyridazine compounds was explored against four cancer cell lines in\u00a0vitro. Indenopyridazine\u2010thiazolin\u20104\u2010one hybrid\n                    <jats:bold>11c<\/jats:bold>\n                    exhibited the highest cytotoxicity against HepG2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20097.43\u2009\u03bcM) and MCF\u20107 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20094.37\u2009\u03bcM). Their IC\n                    <jats:sub>50<\/jats:sub>\n                    values were very close to the reference drug 5\u2010fluorouracil. Also, compound\n                    <jats:bold>7b<\/jats:bold>\n                    was found to show a very strong cytotoxic effect against HepG2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200910.20\u2009\u03bcM) and MCF\u20107 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20097.39\u2009\u03bcM). Moreover, molecular docking indicated that compounds\n                    <jats:bold>11b<\/jats:bold>\n                    ,\n                    <jats:bold>7b<\/jats:bold>\n                    , and\n                    <jats:bold>11c<\/jats:bold>\n                    had the best docking score against vascular endothelial growth factor recetor\u20102 (VEGFR\u20102) which is the potential target predicted by target fishing.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70203","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:13:57Z","timestamp":1762928037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis, Cytotoxic Activity, and Molecular Docking Study of New Thiazole\u2010Incorporated Indenopyridazine Derivatives as Potential Antiproliferative Drugs"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8845-2786","authenticated-orcid":false,"given":"Alaa M.","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy Umm Al\u2010Qura University  Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan I.","family":"Alkubaysi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy Umm Al\u2010Qura University  Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5942-1411","authenticated-orcid":false,"given":"Mariam","family":"Mojally","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy Umm Al\u2010Qura University  Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amgad","family":"Albohy","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy University of Sharjah  Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussni","family":"Muathen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy Umm Al\u2010Qura University  Makkah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3184\/0308234054213735"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2020.11.020"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2023.2166036"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.140976"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1385272827666230809094221"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.1c00057"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00003"},{"key":"e_1_2_7_9_1","first-page":"560","article-title":"Azoles. 17. 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