{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:11:45Z","timestamp":1789999905022,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is a leading cause of cancer\u2010related mortality worldwide, driven mainly by chronic hepatitis infections and metabolic disorders, which highlights the urgent need for novel therapeutic strategies. Sirtuins, particularly SIRT1 are crucial in HCC pathogenesis, making it a promising drug target. Indole\u2010based molecules show potential as therapeutic agents by interacting with key proteins like sirtuins involved in cancer progression. In this study, we designed and synthesized novel indole\u2010based small molecules and investigated their potential sirtuin inhibitory action and anticancer activity on HCC cell lines. Four of the twenty\u2010eight tested small molecules on different cancer types were selected (\n                    <jats:bold>4\u2009g<\/jats:bold>\n                    ,\n                    <jats:bold>4\u2009h<\/jats:bold>\n                    ,\n                    <jats:bold>4o<\/jats:bold>\n                    , and\n                    <jats:bold>7j<\/jats:bold>\n                    ) based on their structure\u2013activity relationship and studied on a panel of HCC cell lines. Compounds had active drug\u2010target interactions with SIRT1 or SIRT2 based on DEEPScreen DTI predictions and docking studies which confirmed that\n                    <jats:bold>4o<\/jats:bold>\n                    ,\n                    <jats:bold>4\u2009g<\/jats:bold>\n                    , and\n                    <jats:bold>7j<\/jats:bold>\n                    were most potent in their interaction with SIRT1. Compound\n                    <jats:bold>4\u2009g<\/jats:bold>\n                    caused the highest sirtuin activity inhibition in vitro and induced G1 arrest and apoptosis in HCC cell lines.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70008","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T03:01:59Z","timestamp":1729479719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Design, synthesis, and evaluation of novel Indole\u2010Based small molecules as sirtuin inhibitors with anticancer activities"],"prefix":"10.1002","volume":"85","author":[{"given":"Busra","family":"Binarci","sequence":"first","affiliation":[{"name":"Department of Biological Sciences METU  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ensar Korkut","family":"Kilic","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy Gazi University  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunca","family":"Dogan","sequence":"additional","affiliation":[{"name":"Biological Data Science Lab, Department of Computer Engineering Hacettepe University  Ankara Turkiye"},{"name":"Department of Bioinformatics, Graduate School of Health Sciences Hacettepe University  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rengul","family":"Cetin Atalay","sequence":"additional","affiliation":[{"name":"Cancer Systems Biology Laboratory, Department of Health Informatics Graduate School of Informatics, METU  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3381-5463","authenticated-orcid":false,"given":"Deniz Cansen","family":"Kahraman","sequence":"additional","affiliation":[{"name":"Cancer Systems Biology Laboratory, Department of Health Informatics Graduate School of Informatics, METU  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9929-6467","authenticated-orcid":false,"given":"Sultan","family":"Nacak Baytas","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Faculty of Pharmacy Gazi University  Ankara Turkiye"},{"name":"Department of Pharmaceutical Chemistry, Graduate School of Health Sciences Gazi University  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"issue":"1","key":"e_1_2_7_2_1","first-page":"3","article-title":"Differential SIRT1 expression in hepatocellular carcinomas and cholangiocarcinoma of the liver","volume":"45","author":"Al\u2010Bahrani R.","year":"2015","journal-title":"Annals of Clinical and Laboratory 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