{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:46:48Z","timestamp":1788580008396,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009697","name":"Hashemite University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009697","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Unregulated epigenetic modifications, including histone acetylation\/deacetylation mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), contribute to cancer progression. HDACs, often overexpressed in cancer, downregulate tumor suppressor genes, making them crucial targets for treatment. This work aimed to develop non\u2010hydroxamate benzoic acid\u2013based HDAC inhibitors (HDACi) with comparable effect to the currently four FDA\u2010approved HDACi, which are known for their poor solubility, poor distribution, and significant side effects. All compounds were structurally verified using FTIR,\n                    <jats:sup>1<\/jats:sup>\n                    HNMR,\n                    <jats:sup>13<\/jats:sup>\n                    CNMR, and mass spectrometry. In silico analysis showed that compound\n                    <jats:bold>A3bn<\/jats:bold>\n                    (3\u2010chloro\u20104\u2010((2\u2010(2\u2010(4\u2010hydroxybenzylidene) hydrazinyl)\u20102\u2010oxoethyl)amino)benzoic acid) has strong binding affinity towards HDAC2, HDAC6, and HDAC8 and exhibits molecular similarity to trichostatin and SAHA (HDACi).\n                    <jats:bold>A3bn<\/jats:bold>\n                    achieved IC\n                    <jats:sub>50<\/jats:sub>\n                    values comparable to SAHA against MCF\u20107 (20.3 vs. 39.2\u00a0\u00b5M) and K562 (42.0 vs. 36.1\u00a0\u00b5M) cancer cells. Western blot analysis confirmed that\n                    <jats:bold>A3bn<\/jats:bold>\n                    inhibited H3 and H4 deacetylation. Additionally,\n                    <jats:bold>A3bn<\/jats:bold>\n                    induced the extrinsic apoptotic pathway via caspase 8 activation, leading to cell death. Its enhanced activity across HDAC isoforms may result from its hydrophilic linker, facilitating zinc coordination. In conclusion,\n                    <jats:bold>A3bn<\/jats:bold>\n                    demonstrated efficacy similar to FDA\u2010approved HDACi and represents a promising candidate for further optimization. Future studies will focus on structural modifications to enhance potency and selectivity at lower concentrations.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501492","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T19:51:02Z","timestamp":1756842662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis, In Silico, and Biological Evaluation of Non\u2010Hydroxamate Benzoic Acid\u2013Based Derivatives as Potential Histone Deacetylase Inhibitors (HDACi)"],"prefix":"10.1002","volume":"22","author":[{"given":"Nedaa A. Abd","family":"Al Rahim","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry College of Pharmacy, University of Baghdad  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-417X","authenticated-orcid":false,"given":"Ammar A. Razzak","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry College of Pharmacy, University of Baghdad  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-1944","authenticated-orcid":false,"given":"Lubna H.","family":"Tahtamouni","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Faculty of Science The Hashemite University  Zarqa Jordan"},{"name":"Department of Biochemistry and Molecular Biology College of Natural Sciences, Colorado State University  Fort Collins Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa M.","family":"Bawadi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Faculty of Allied Sciences Zarqa University  Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayah Y.","family":"Almasri","sequence":"additional","affiliation":[{"name":"Department of Basic Dental Sciences Faculty of Dentistry The Hashemite University  Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marya A.","family":"Hamad","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Faculty of Science The Hashemite University  Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour A.","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Faculty of Science The Hashemite University  Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem R.","family":"Yasin","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology Faculty of Science The Hashemite University  Zarqa Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman M.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Cairo University  Cairo Egypt"},{"name":"Infection Control and Epidemiology Surveillance Unit Aweash El\u2010Hagar Family Medicine Center, Ministry of Health and Population (MOHP)  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.01.036"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018713"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2015.07.005"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026831"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01188.x"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25747"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-018-0773-9"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23265"},{"key":"e_1_2_13_10_1","article-title":"Oxadiazole Derivatives: Histone Deacetylase Inhibitors in Anticancer Therapy and Drug Discovery","volume":"5","author":"Matore B. 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