{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:26:12Z","timestamp":1787163972716,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["2017R1A5A2015541"],"award-info":[{"award-number":["2017R1A5A2015541"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007224","name":"National Foundation for Science and Technology Development","doi-asserted-by":"publisher","award":["104.01\u20102019.300"],"award-info":[{"award-number":["104.01\u20102019.300"]}],"id":[{"id":"10.13039\/100007224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In our continuing search for novel small\u2010molecule anticancer agents, we designed and synthesized a series of novel (\n                    <jats:italic>E<\/jats:italic>\n                    )\u2010\n                    <jats:italic>N'<\/jats:italic>\n                    \u2010(3\u2010allyl\u20102\u2010hydroxy)benzylidene\u20102\u2010(4\u2010oxoquinazolin\u20103(4\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010yl)acetohydrazides (\n                    <jats:bold>5<\/jats:bold>\n                    ), focusing on the modification of substitution in the quinazolin\u20104(3\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC\u20103, prostate cancer; NCI\u2010H23, lung cancer). The most potent compound\n                    <jats:bold>5l<\/jats:bold>\n                    displayed cytotoxicity up to 213\u2010fold more potent than 5\u2010fluorouracil and 87\u2010fold more potent than PAC\u20101, the first procaspase\u2010activating compound. Structure\u2013activity relationship analysis revealed that substitution of either electron\u2010withdrawing or electron\u2010releasing groups at positions 6 or 7 on the quinazolin\u20104(3\n                    <jats:italic>H<\/jats:italic>\n                    )\u20104\u2010one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound\n                    <jats:bold>5l<\/jats:bold>\n                    was found to activate the caspase activity by 291% in comparison to PAC\u20101, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase\u20103 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for\n                    <jats:bold>5l<\/jats:bold>\n                    provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent.\n                  <\/jats:p>","DOI":"10.1002\/ardp.202100216","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T14:15:25Z","timestamp":1634825725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Design, synthesis, and evaluation of novel (E)\u2010\n                    <i>N<\/i>\n                    '\u2010(3\u2010allyl\u20102\u2010hydroxy)benzylidene\u20102\u2010(4\u2010oxoquinazolin\u20103(4\n                    <i>H<\/i>\n                    )\u2010yl)acetohydrazides as antitumor agents"],"prefix":"10.1002","volume":"355","author":[{"given":"Do T. M.","family":"Dung","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Hanoi University of Pharmacy Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun J.","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duong T.","family":"Anh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Hanoi University of Pharmacy Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham\u2010The","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Hanoi University of Pharmacy Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le D.","family":"Huy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Hanoi University of Pharmacy Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye W.","family":"Jun","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Hee","family":"Kwon","sequence":"additional","affiliation":[{"name":"Korea Research Institute of Bioscience and Biotechnology Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Young Ji","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chungbuk National University Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong S.","family":"Kang","sequence":"additional","affiliation":[{"name":"Korea Research Institute of Bioscience and Biotechnology Cheongju Chungbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-203X","authenticated-orcid":false,"given":"Truong T.","family":"Tung","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy PHENIKAA University Hanoi Vietnam"},{"name":"PHENIKAA Institute for Advanced Study (PIAS) PHENIKAA University Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan T. 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