{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:42:43Z","timestamp":1792676563153,"version":"4.5.0"},"reference-count":76,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study modified the solvent\u2010exposed region of sunitinib by replacing its diethylaminoethyl tail with linear and heterocyclic amines, guided by lipophilicity, steric, and electronic considerations to enhance the anticancer activity and selectivity. Sunitinib and its 20 derivatives, including 14 new compounds (\n                    <jats:bold>4a<\/jats:bold>\n                    ,\n                    <jats:bold>4c<\/jats:bold>\n                    ,\n                    <jats:bold>4d<\/jats:bold>\n                    ,\n                    <jats:bold>4g\u20134i, 5a<\/jats:bold>\n                    ,\n                    <jats:bold>5b<\/jats:bold>\n                    ,\n                    <jats:bold>7a\u20137e<\/jats:bold>\n                    , and\n                    <jats:bold>8<\/jats:bold>\n                    ) and 6 known compounds (\n                    <jats:bold>4b<\/jats:bold>\n                    ,\n                    <jats:bold>4e\u20134f<\/jats:bold>\n                    ,\n                    <jats:bold>5c\u20135d<\/jats:bold>\n                    , and\n                    <jats:bold>6<\/jats:bold>\n                    ), were successfully synthesized. The cytotoxic effects of sunitinib and its derivatives were evaluated against three human cancer cell lines (HeLa, SH\u2010SY5Y, and HepG2) and one normal cell line (L929) using the MTT assay. Sunitinib exhibited the strongest cytotoxicity toward SH\u2010SY5Y neuroblastoma cells, with an IC\u2085\u2080 of 3.88\u2009\u00b5M. Among the derivatives, compound\n                    <jats:bold>5b<\/jats:bold>\n                    showed the highest potency with an IC\u2085\u2080 of 4.28\u2009\u00b5M against SH\u2010SY5Y. Compound\n                    <jats:bold>6<\/jats:bold>\n                    displayed the highest selectivity index (SI\u2009\u2265\u20095) for HeLa, indicating good selectivity toward cancer over normal cells. Overall, these results suggest that targeted modification of the solvent\u2010exposed region in sunitinib can improve anticancer activity without toxicity against normal cell lines, with compound\n                    <jats:bold>5b<\/jats:bold>\n                    emerging as a promising lead for further development, particularly against neuroblastoma. The solvent\u2010exposed region is strategic for drug development, allowing modifications that improve affinity, selectivity, solubility, and pharmacokinetics without disrupting ligand\u2010protein interactions.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70168","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T10:53:27Z","timestamp":1766228007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the Anticancer Activity of Sunitinib Derivatives Through Modifications in Solvent\u2010Exposed Regions: Synthesis, In Vitro Evaluation, and Computational Studies"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-9459","authenticated-orcid":false,"given":"Robby Gus","family":"Mahardika","sequence":"first","affiliation":[{"name":"Doctoral Program of Chemistry Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung Bandung West Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ade","family":"Danova","sequence":"additional","affiliation":[{"name":"Organic Chemistry Division Group Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung Bandung West Java Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanat","family":"Aonbangkhen","sequence":"additional","affiliation":[{"name":"Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science Chulalongkorn University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaruwan","family":"Chatwichien","sequence":"additional","affiliation":[{"name":"Program in Chemical Sciences Chulabhorn Graduate Institute Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutthida","family":"Wongsuwan","sequence":"additional","affiliation":[{"name":"Center of Excellence in Natural Products 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