{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:37:52Z","timestamp":1792373872733,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008347","name":"Bezmialem Vak\u0131f \u00dcniversitesi","doi-asserted-by":"publisher","award":["20230211"],"award-info":[{"award-number":["20230211"]}],"id":[{"id":"10.13039\/501100008347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Herein, new derivatives of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>\u03b2\u2010<\/jats:italic>\n                    unsaturated ketones based on oleanolic acid (\n                    <jats:bold>4\u2009a<\/jats:bold>\n                    \u2013\n                    <jats:bold>i<\/jats:bold>\n                    ) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the\n                    <jats:italic>in\u2005vitro<\/jats:italic>\n                    cytotoxic study, title compounds (\n                    <jats:bold>4\u2009a<\/jats:bold>\n                    \u2013\n                    <jats:bold>i<\/jats:bold>\n                    ) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC\n                    <jats:sub>50<\/jats:sub>\n                    values on PC3\u2005cell lines were\n                    <jats:bold>4\u2009b<\/jats:bold>\n                    (7.785\u2005\u03bcM),\n                    <jats:bold>4\u2009c<\/jats:bold>\n                    (8.869\u2005\u03bcM), and\n                    <jats:bold>4\u2009e<\/jats:bold>\n                    (8.765\u2005\u03bcM). The results of the ADME calculations showed that the drug\u2010likeness parameters were within the defined ranges according to Lipinski's and Jorgensen's rules. For the most potent compounds\n                    <jats:bold>4\u2009b<\/jats:bold>\n                    ,\n                    <jats:bold>4\u2009c<\/jats:bold>\n                    , and\n                    <jats:bold>4\u2009e<\/jats:bold>\n                    , a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound\n                    <jats:bold>4\u2009b<\/jats:bold>\n                    had the highest calculated affinity for PARP1, while compound\n                    <jats:bold>4\u2009c<\/jats:bold>\n                    had higher affinities for mTOR and PI3K. The MM\u2010GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50\u2005ns molecular dynamics simulation was performed to study the behavior of protein target complexes under\n                    <jats:italic>in silico<\/jats:italic>\n                    physiological conditions.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202301089","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T03:12:04Z","timestamp":1692414724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Synthesis and Anticancer Activity of Novel Derivatives of \u03b1,\u03b2\u2010Unsaturated Ketones Based on Oleanolic Acid:\n                    <i>in Vitro<\/i>\n                    and\n                    <i>in Silico<\/i>\n                    Studies against Prostate Cancer Cells"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8333-035X","authenticated-orcid":false,"given":"Halil","family":"\u015eenol","sequence":"first","affiliation":[{"name":"Bezmialem Vakif University Faculty of Pharmacy, Department of Pharmaceutical Chemistry  34093 Fatih Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansour","family":"Ghaffari\u2010Moghaddam","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University Faculty of Pharmacy, Department of Pharmaceutical Chemistry  34093 Fatih Istanbul T\u00fcrkiye"},{"name":"University of Zabol Faculty of Science, Department of Chemistry  Zabol 98615-538 Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eeyma","family":"Bulut","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University Institute of Health Sciences, Department of Biotechnology  34093 Fatih Istanbul T\u00fcrkiye"},{"name":"Bezmialem Vakif University Faculty of Medicine, Department of Medical Biology  34093 Fatih Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahri","family":"Akba\u015f","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University Faculty of Medicine, Department of Medical Biology  34093 Fatih Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aytekin","family":"K\u00f6se","sequence":"additional","affiliation":[{"name":"Aksaray University Faculty of Science and Letters, Department of Chemistry  68100 Aksaray T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcla\u00e7t\u0131","family":"Top\u00e7u","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University Faculty of Pharmacy, Department of Pharmacognosy &amp; Phytochemistry Chemistry  34093 Fatih Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2022.154288"},{"key":"e_1_2_10_2_1","unstructured":"\u00a0"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.07.003"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013500"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106145"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105575"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01598-0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01061-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901183116"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106412"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9040034"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2022.116707"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.115030"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106356"},{"key":"e_1_2_10_15_1","unstructured":"\u00a0"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222112000"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113007"},{"key":"e_1_2_10_18_1","unstructured":"\u00a0"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2020.114389"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.2c00798"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-023-03031-z"},{"key":"e_1_2_10_22_2","volume":"4","author":"\u015eenol H.","year":"2022","journal-title":"Res. 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