{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:59:44Z","timestamp":1789721984424,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high\u2010risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL\u201060. Novel <jats:italic>N<\/jats:italic>\u2010(1<jats:italic>H<\/jats:italic>\u2010indol\u20101\u2010yl)\u20105,5,8,8\u2010tetramethyl\u20105,6,7,8\u2010tetrahydronaphthalene\u20102\u2010carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound <jats:bold>5<\/jats:bold>, were determined in K562 chronic myeloid leukemia and HL\u201060 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound <jats:bold>5<\/jats:bold> more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound <jats:bold>5<\/jats:bold> induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0\/G1 was also increased with compound <jats:bold>5<\/jats:bold> treatment. Important modulator proteins of cell proliferation p\u2010ERK, p\u2010AKT, and p\u2010m\u2010TOR were also found to be inhibited with compound <jats:bold>5<\/jats:bold> treatment. Collectively, our results reveal compound <jats:bold>5<\/jats:bold>, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia.<\/jats:p>","DOI":"10.1111\/fcp.12876","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:54:30Z","timestamp":1674521670000},"page":"557-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel indole retinoid derivative induces apoptosis and cell cycle arrest and modulates AKT and ERK signaling in HL\u201060 cells"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-0165","authenticated-orcid":false,"given":"A. Selen","family":"Gurkan\u2010Alp","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmaceutical Chemistry Ankara University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2482-0359","authenticated-orcid":false,"given":"Arzu Z.","family":"Karabay","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Biochemistry Ankara University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4679-9079","authenticated-orcid":false,"given":"Asli","family":"Koc","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Biochemistry Ankara University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-7314","authenticated-orcid":false,"given":"Erdem","family":"Buyukbingol","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmaceutical Chemistry Ankara University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272\u2010014\u20100438\u2010x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12581"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871521409666170412122811"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4067\/s0717\u201097072020000204900"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520615666150520144217"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.10.013"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12813"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2340"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.167502"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010011110\u2010130303"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402718"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2016.02.008"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802612799436687"},{"key":"e_1_2_11_15_1","first-page":"39","article-title":"DNA binding and antiproliferative effects of some benzimidazole retinoids","volume":"34","author":"Piskin AK","year":"2009","journal-title":"Turkish Journal of Biochemistry\u2010Turk Biyokimya Dergisi"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.21577\/0103\u20105053.20170119"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.200400932"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.11.021"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00044a014"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo01075a008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1515\/HC.2001.7.5.455"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.200500177"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.66"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21082907"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1005"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.09.003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2013.2520"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.429"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.4.1520.bloodjournal8741520"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.07.024"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2021.12842"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.10.3343"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073510"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26020295"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104331"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011960.pub2"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.03.008"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29081"},{"issue":"14","key":"e_1_2_11_39_1","first-page":"3163","article-title":"Retinoic acid induced mitogen\u2010activated protein (MAP)\/extracellular signal\u2010regulated kinase (ERK) kinase\u2010dependent MAP kinase activation needed to elicit HL\u201060 cell differentiation and growth arrest","volume":"58","author":"Yen A","year":"1998","journal-title":"Cancer Res"},{"issue":"7","key":"e_1_2_11_40_1","first-page":"532","article-title":"Retinoic acid differentially regulates cancer cell proliferation via dose\u2010dependent modulation of the mitogen\u2010activated protein kinase pathway","volume":"1","author":"Crowe DL","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2019.1682579"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.09.120"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1450749"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12876","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/fcp.12876","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12876","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T17:24:13Z","timestamp":1692638653000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.12876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,30]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1111\/fcp.12876"],"URL":"https:\/\/doi.org\/10.1111\/fcp.12876","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,30]]},"assertion":[{"value":"2022-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}