{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:43:04Z","timestamp":1785861784920,"version":"3.56.0"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Designing new compounds from existing chemotherapeutic drugs to enhance inhibitory effects on tumor cells while overcoming multidrug resistance is one of the important strategies for new drug discovery in medicinal chemistry. A new series of urea and thiourea derivatives based on Lenalidomide as potential anticancer agents have been designed and synthesized.\n                    <jats:italic>In vitro<\/jats:italic>\n                    anticancer activity assay against Caki cancer cells and HUVEC endothelial cells revealed that 1\u2010(4\u2010methylphenyl)\u20103\u2010[2\u2010(2,6\u2010dioxopiperidin\u20103\u2010yl)\u20101\u2010oxoisoindolin\u20104\u2010yl]urea (\n                    <jats:bold>11<\/jats:bold>\n                    ) exhibited the highest anticancer activity and selectivity in the series with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 9.88 and 179.03\u2009\u00b5M, respectively. Among the compounds,\n                    <jats:bold>11<\/jats:bold>\n                    showed significant HDAC1 inhibiton of 68.02\u2009\u00b1\u20092.44% at 10\u2009\u00b5M concentration. TGF\u2010\u03b2, Bax, Bcl\u20102 protein levels and scratch assay were analyzed in Caki cells. As a result, compound\n                    <jats:bold>11<\/jats:bold>\n                    induced apoptosis in Caki cells. In this study, it has been demonstrated that compound\n                    <jats:bold>11<\/jats:bold>\n                    can be a lead compound for further detailed investigation in renal cancer treatment. Through molecular docking studies, it was determined that the most active compound,\n                    <jats:bold>11<\/jats:bold>\n                    , forms stable interactions with key residues in the enzyme's active site, particularly engaging in hydrogen bonds with GLY149 and coordinating with the zinc ion in the HDAC1 active site. These interactions are crucial for the observed inhibitory activity. Molecular dynamics simulation revealed the binding event of the most active compound with class I histone deacetylase and the stability of the complex in a biological environment.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70079","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T06:42:02Z","timestamp":1733121722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis, Biological Evaluation and in Silico Studies of Novel Urea\/Thiourea Derivatives of Lenalidomide"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4569-008X","authenticated-orcid":false,"given":"Fatih","family":"Tok","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Marmara University Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bur\u00e7in \u0130rem","family":"Abas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine Ayd\u0131n Adnan Menderes University Ayd\u0131n Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faika","family":"Ba\u015fo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy European University of Lefke Northern Cyprus Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9325-3757","authenticated-orcid":false,"given":"\u00d6zge","family":"\u00c7evik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine Ayd\u0131n Adnan Menderes University Ayd\u0131n Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi","family":"Karaku\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Istanbul Aydin University Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-5145","authenticated-orcid":false,"given":"Abdulilah","family":"Ece","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Biruni University Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"issue":"5","key":"e_1_2_9_2_1","first-page":"308","article-title":"Lenalidomide (Revlimid): A Thalidomide Analogue in Combination With Dexamethasone For the Treatment of All Patients With Multiple Myeloma","volume":"41","author":"Cruz M. 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