{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:21:44Z","timestamp":1767086504025,"version":"3.48.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","award":["CMU113\u2010S\u201047"],"award-info":[{"award-number":["CMU113\u2010S\u201047"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Considerable effort has been put into developing YC\u20101 (lificiguat), an indazole derivative with dual targets including soluble guanylate cyclase (sGC) and hypoxia\u2010inducible factor\u20101 (HIF\u20101), as new drug molecules with increased potency. Building on our previous findings, this structure\u2013activity relationship study focused on the substitutability of 4\n                    <jats:italic>H<\/jats:italic>\n                    \u2010furo[3,2\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]indole derivatives. (4\n                    <jats:italic>H<\/jats:italic>\n                    \u2010thieno[3,2\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]indol\u20103\u2010yl)methanol was identified as the chemical skeleton for developing tumoricidal compounds. Notably, the chemotypes exhibited selective cytotoxicity toward cancer cell lines without affecting normal human fibroblasts. Among these compounds, (5\u2010((3\u2010(hydroxymethyl)\u20104\n                    <jats:italic>H<\/jats:italic>\n                    \u2010thieno[3,2\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]indol\u20104\u2010yl)methyl)furan\u20102\u2010yl)methanol (\n                    <jats:bold>28i<\/jats:bold>\n                    ) emerged as the most promising candidate, demonstrating robust antiproliferative efficacy against A498 renal carcinoma cells, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 21.0\u2009nM. Moreover,\n                    <jats:bold>28i<\/jats:bold>\n                    induced significant apoptosis in A498 cells at a concentration of 50\u2009nM, accompanied by cell cycle arrest in the G\n                    <jats:sub>2<\/jats:sub>\n                    \/M phase. Western blot analysis of apoptosis\u2010related proteins indicated that\n                    <jats:bold>28i<\/jats:bold>\n                    induces mitochondrial\u2010mediated apoptosis. Molecular docking studies on YC\u20101, 4\n                    <jats:italic>H<\/jats:italic>\n                    \u2010furo[3,2\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]indole derivative\n                    <jats:bold>A<\/jats:bold>\n                    , and\n                    <jats:bold>28i<\/jats:bold>\n                    demonstrated that compound\n                    <jats:bold>28i<\/jats:bold>\n                    exhibited the highest docking score and possesses high potential for inhibiting HIF\u20101 by targeting the ARNT\u2010dependent pathway. The structural framework of (4\n                    <jats:italic>H<\/jats:italic>\n                    \u2010thieno[3,2\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]indol\u20103\u2010yl)methanol makes it a promising candidate for cancer therapy.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70233","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T05:45:56Z","timestamp":1767073556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Biological Evaluation of (\n                    <scp>4<\/scp>\n                    <i>H<\/i>\n                    \u2010Thieno[3,2\u2010\n                    <i>b<\/i>\n                    ]indol\u20103\u2010yl)methanol as a Tumoricidal Scaffold for an Antineoplastic 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