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We designed and synthesized a series of 22 <jats:italic>N<\/jats:italic>\u2010hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a <jats:italic>p<\/jats:italic>\u2010hydroxycinnamate linker, and hydroxamic acids as the zinc\u2010binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP\u20101 cell proliferation. Compounds <jats:bold>7d<\/jats:bold> and <jats:bold>7p<\/jats:bold>, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell\u2010cycle progression as vorinostat and induce apoptosis in THP\u20101 cells. Furthermore, compounds <jats:bold>7d<\/jats:bold> and <jats:bold>7p<\/jats:bold> were demonstrated to inhibit HDAC class I and II in THP\u20101 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn<jats:sup>2+<\/jats:sup> ion chelation by the hydroxamate group.<\/jats:p>","DOI":"10.1002\/ardp.202400889","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T05:07:30Z","timestamp":1743570450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["New potent <i>N<\/i>\u2010hydroxycinnamamide\u2010based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP\u20101 leukaemia cells"],"prefix":"10.1002","volume":"358","author":[{"given":"Magdalena","family":"Onuscakova","sequence":"first","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2854-511X","authenticated-orcid":false,"given":"Tereza","family":"Kauerova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Fialova","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-5366","authenticated-orcid":false,"given":"Hana","family":"Pizova","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Garaj","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Comenius University Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Kemka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Comenius University Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-5860","authenticated-orcid":false,"given":"Vladimir","family":"Frecer","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry of Drugs, Faculty of Pharmacy Comenius University Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-1528","authenticated-orcid":false,"given":"Peter","family":"Kollar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-3810","authenticated-orcid":false,"given":"Pavel","family":"Bobal","sequence":"additional","affiliation":[{"name":"Department of Chemical Drugs, Faculty of Pharmacy Masaryk University Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-021-00721-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13148-010-0017-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01197-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp220"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170152"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2016.04.001"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0675-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyw058"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-019-0138-5"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.140"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.22"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03794-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-019-0095-0"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.36"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.578011"},{"issue":"2","key":"e_1_2_9_17_1","first-page":"166","volume":"3","author":"Kim H. 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