{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:25Z","timestamp":1792003705507,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:p>\n                    The target\u2010oriented synthesis of diethylene glycol\u2010linked bis\u2010imidazo\u2010 and bis\u2010thiazolo ring\u2010fused mono\u2010, bi\u2010, and tricyclic derivatives was accomplished using inexpensive reagents, bis\u2010phenacyl bromide derivative\n                    <jats:bold>4<\/jats:bold>\n                    , and thiosemicarbazone\n                    <jats:bold>6<\/jats:bold>\n                    . The diethylene glycol\u2010linked architectures included bis(thiazolo[3,2\u2010\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrimidinone) derivatives\n                    <jats:bold>8a,b<\/jats:bold>\n                    , bis(imidazo\u2010azole) derivatives\n                    <jats:bold>12\u201014<\/jats:bold>\n                    , bis(imidazo\u2010thiazole) derivatives\n                    <jats:bold>17,18<\/jats:bold>\n                    , and bis\u2010thiazoles\n                    <jats:bold>20a\u2010g<\/jats:bold>\n                    . Cytotoxic evaluation against liver, lung, colon, and prostate human tumor cell lines found remarkable selectivity to hepatocellular carcinoma (HepG2) cells. The most potent bis\u2010imidazo\u2010 and bis\u2010thiazolo\u2010fused derivatives\n                    <jats:bold>8a,b<\/jats:bold>\n                    ,\n                    <jats:bold>12<\/jats:bold>\n                    and\n                    <jats:bold>13<\/jats:bold>\n                    demonstrated cytotoxicity against HepG2 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    6.8\u201317.8\u2009\u00b5M) with exceptional selectivity (SI 5.6\u201314.6) compared with cisplatin (SI 2.4). Further screening of their VEGFR\u20102 TK and FGFR\u20102 TK inhibition showed that\n                    <jats:bold>8a<\/jats:bold>\n                    had moderate activity, whereas phenyl\u2010substituted derivative\n                    <jats:bold>8b<\/jats:bold>\n                    displayed promising anti\u2010VEGFR\u20102 and remarkable anti\u2010FGFR\u20102 activities, with IC\n                    <jats:sub>50<\/jats:sub>\n                    0.19\u2009\u00b1\u20090.01 and 0.03\u2009\u00b1\u20090.01\u2009\u00b5M, respectively, compared with the reference drugs sorafenib (IC\n                    <jats:sub>50<\/jats:sub>\n                    0.12\u2009\u00b1\u20090.01) and staurosporine (IC\n                    <jats:sub>50<\/jats:sub>\n                    0.03\u2009\u00b1\u20090.01\u2009\u00b5M). The inhibition of VEGFR\u20102 and FGFR\u20102 TKs was supported by molecular docking studies, with compound\n                    <jats:bold>8b<\/jats:bold>\n                    showing binding affinity to the VEGFR\u20102 and FGFR\u20102 ATP binding pockets. Pharmacokinetics and ADMET drug\u2010likeness evaluation indicated that bis(thiazolo[3,2\u2010\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrimidinone) derivatives\n                    <jats:bold>8a<\/jats:bold>\n                    and\n                    <jats:bold>8b<\/jats:bold>\n                    have drug\u2010like properties.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70504","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:47:24Z","timestamp":1790747244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diethylene Glycol\u2010Linked Ring\u2010Fused Bis\u2010Azoles: Target\u2010Oriented Synthesis, In Silico Screening, and Antitumor Activity"],"prefix":"10.1002","volume":"21","author":[{"given":"Sami A.","family":"Al\u2010Hussain","sequence":"first","affiliation":[{"name":"Department of Chemistry Faculty of Science Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-2155","authenticated-orcid":false,"given":"Abdulrahman S.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Science and Humanities\u2010Dawadmi Shaqra University  Sajir Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-8497","authenticated-orcid":false,"given":"Zeinab A.","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Egyptian Drug Authority (EDA)  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyaa S. Abdel","family":"Halim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Science Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-9202","authenticated-orcid":false,"given":"Magdi E. A.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1263-138X","authenticated-orcid":false,"given":"Mark C.","family":"Bagley","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Sussex  Brighton East Sussex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8304-736X","authenticated-orcid":false,"given":"Refaie M.","family":"Kassab","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science Cairo University  Giza 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