{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:13:05Z","timestamp":1788221585499,"version":"build-2803163510"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004071","name":"Khon Kaen University","doi-asserted-by":"publisher","award":["2569 (FF69)"],"award-info":[{"award-number":["2569 (FF69)"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anthraquinones are well-recognized anticancer scaffolds, but their systematic optimization within an HDAC-inspired pharmacophore framework remains limited. Since HDAC dysregulation is closely associated with cancer progression, chromatin remodeling, and cell-cycle control, applying this design strategy to anthraquinone scaffolds may provide a useful route toward new anticancer analogs. Herein, a focused series of anthraquinone sulfonamide and carboxamide analogs were designed using an extended cap-connecting unit (CU)\u2013linker\u2013terminal zinc-binding group (ZBG) concept. The anthraquinone core was employed as a cap-like scaffold, sulfonamide or carboxamide was employed as the CU, amino acid-derived fragments were employed as linkers, and methyl ester, carboxylic acid, or hydrazide groups were employed as terminal ZBG-like functionalities. Cytotoxicity screening identified sulfonamide hydrazides as the most active subgroup, with 4a showing potent activity against A549 and HeLa cells (IC50 = 5.18 and 6.36 \u03bcM, respectively). In contrast, 8d exhibited moderate cytotoxicity against HeLa cells (IC50 = 9.43 \u03bcM) and low toxicity toward Vero cells (IC50 &amp;gt; 100 \u03bcM). At 100 \u03bcM, preliminary single-concentration screening showed that 4a inhibited HDAC activity in the HeLa nuclear extract and HDAC2 by 16.46% and 14.59%, respectively, whereas 8d produced 64.56% and 38.08% inhibition, respectively. Cellular changes in Ac\u2013H3 and p21 did not fully parallel these biochemical results. Both compounds induced cell-line-dependent apoptosis and cell-cycle perturbation. Exploratory docking predicted Zn2+ coordination by 8d in HDAC2, while in silico ADMET analysis suggested a more favorable physicochemical profile for 4a. Overall, 4a and 8d are identified as cytotoxic anthraquinone analogs with distinct, preliminary, and compound-dependent HDAC-modulating effects, providing a rationale for further mechanistic investigation.<\/jats:p>","DOI":"10.1021\/acsomega.6c04719","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:02:03Z","timestamp":1786647723000},"page":"49881-49898","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Biological Evaluation of Anthraquinone\nSulfonamide and Carboxamide Analogs: Cytotoxicity and Preliminary\nHDAC-Modulating Effects"],"prefix":"10.1021","volume":"11","author":[{"given":"Jiratthakan","family":"Prathumchat","sequence":"first","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siripit","family":"Pitchuanchom","sequence":"additional","affiliation":[{"name":"Mahasarakham University , , ,","place":["Maha Sarakham, Thailand, 44150"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadaporn","family":"Leerat","sequence":"additional","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narissara","family":"Namwan","sequence":"additional","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulsiri","family":"Senawong","sequence":"additional","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanaset","family":"Senawong","sequence":"additional","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0108-0204","authenticated-orcid":true,"given":"Chanokbhorn","family":"Phaosiri","sequence":"additional","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-5917","authenticated-orcid":true,"given":"Mongkol","family":"Nontakitticharoen","sequence":"additional","affiliation":[{"name":"Khon Kaen University , , ,","place":["Khon Kaen, Thailand, 40002"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026083119145408100_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN\nestimates of incidence and mortality worldwide for 36 cancers in 185\ncountries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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Chem."},{"key":"2026083119145408100_cit6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/cmdc.201500486","article-title":"Why hydroxamates\nmay not be the best histone deacetylase\ninhibitors\u2500What some may have forgotten or would rather forget?","volume":"11","author":"Shen","year":"2016","journal-title":"ChemMedChem"},{"key":"2026083119145408100_cit7","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1158\/1541-7786.MCR-07-0324","article-title":"Histone\ndeacetylase inhibitors: Overview\nand perspectives","volume":"5","author":"Dokmanovic","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"2026083119145408100_cit8","doi-asserted-by":"publisher","first-page":"369","DOI":"10.3390\/ijms23010369","article-title":"Synthesis, molecular\ndocking and\nbiological characterization of pyrazine linked 2-aminobenzamides as\nnew class I selective histone deacetylase (HDAC) inhibitors with anti-leukemic\nactivity","volume":"23","author":"Ibrahim","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026083119145408100_cit9","doi-asserted-by":"publisher","first-page":"497","DOI":"10.2147\/DDDT.S237957","article-title":"Design, synthesis and biological\nevaluation of new HDAC1 and HDAC2 inhibitors endowed with ligustrazine\nas a novel cap moiety","volume":"14","author":"Al-Sanea","year":"2020","journal-title":"Drug Des. Devel. 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Kurz and their semi-synthetic derivatives as\nhistone deacetylase inhibitors","volume":"78","author":"Somsakeesit","year":"2024","journal-title":"J. Nat. Med."},{"key":"2026083119145408100_cit18","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1007\/s00044-025-03418-0","article-title":"Exploring putative\nhistone deacetylase\ninhibitors with antiproliferative activity of chrysin derivatives","volume":"34","author":"Kamloon","year":"2025","journal-title":"Med. Chem. Res."},{"key":"2026083119145408100_cit19","doi-asserted-by":"publisher","first-page":"627","DOI":"10.4155\/fmc-2019-0322","article-title":"Novel anthraquinone\ncompounds as anticancer agents and their potential mechanism","volume":"12","author":"Tian","year":"2020","journal-title":"Future Med. 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Chem."},{"key":"2026083119145408100_cit29","doi-asserted-by":"publisher","first-page":"26926","DOI":"10.1074\/jbc.M113.490706","article-title":"Histone deacetylase (HDAC) inhibitor\nkinetic rate constants correlate with cellular histone acetylation\nbut not transcription and cell viability","volume":"288","author":"Lauffer","year":"2013","journal-title":"J.\nBiol. Chem."},{"key":"2026083119145408100_cit30","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/2472555219883625","article-title":"A comparative\nstudy\nof target engagement assays for HDAC1 inhibitor profiling","volume":"25","author":"Asawa","year":"2020","journal-title":"SLAS Discovery"},{"key":"2026083119145408100_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.201800027","article-title":"Quinazoline-based\nhydroxamic acids: Design, synthesis,\nand evaluation of histone deacetylase inhibitory effects and cytotoxicity","volume":"15","author":"Hieu","year":"2018","journal-title":"Chem. Biodiversity"},{"key":"2026083119145408100_cit32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181081","article-title":"Cisplatin resistance in non-small cell lung cancer\ncells is associated with an abrogation of cisplatin-induced G2\/M cell\ncycle arrest","volume":"12","author":"Sarin","year":"2017","journal-title":"PLoS One"},{"key":"2026083119145408100_cit33","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.bbrc.2016.03.053","article-title":"Cisplatin-induced\napoptosis in non-small-cell lung cancer cells is dependent on Bax-\nand Bak-induction pathway and synergistically activated by BH3-mimetic\nABT-263 in p53 wild-type and mutant cells","volume":"473","author":"Matsumoto","year":"2016","journal-title":"Biochem.\nBiophys. Res. Commun."},{"key":"2026083119145408100_cit34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/862879","article-title":"Mechanisms\nof cisplatin-induced apoptosis and of cisplatin sensitivity: Potential\nof BIN1 to act as a potent predictor of cisplatin sensitivity in gastric\ncancer treatment","volume":"2012","author":"Tanida","year":"2012","journal-title":"Int. J. Surg. Oncol."},{"key":"2026083119145408100_cit35","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1007\/BF02789656","article-title":"The mechanism of cisplatin-induced\napoptosis in HeLa cells","volume":"2","author":"Liu","year":"2005","journal-title":"Chin. J. Clin. Oncol."},{"key":"2026083119145408100_cit36","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1124\/mol.109.055178","article-title":"Cisplatin-induced DNA damage activates replication\ncheckpoint signaling components that differentially affect tumor cell\nsurvival","volume":"76","author":"Wagner","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"2026083119145408100_cit37","doi-asserted-by":"publisher","first-page":"4014","DOI":"10.3390\/molecules27134014","article-title":"HDAC inhibitory\nand anti-cancer activities of curcumin and curcumin derivative CU17\nagainst human lung cancer A549 cells","volume":"27","author":"Namwan","year":"2022","journal-title":"Molecules"},{"key":"2026083119145408100_cit38","doi-asserted-by":"publisher","first-page":"100785","DOI":"10.1016\/j.prmcm.2026.100785","article-title":"6-Shogaol enhances the chemotherapeutic\nefficacy of 5-fluorouracil through apoptosis induction and cell cycle\narrest in MCF-7 breast cancer cells","volume":"18","author":"Sangchang","year":"2026","journal-title":"Pharmacol.\nRes.\u2500Mod. Chin. Med."},{"key":"2026083119145408100_cit39","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.1016\/j.bmcl.2010.03.091","article-title":"Exploration of the\nHDAC2 foot pocket: Synthesis and\nSAR of substituted N-(2-aminophenyl)benzamides","volume":"20","author":"Bressi","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026083119145408100_cit40","doi-asserted-by":"publisher","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web\ntool to evaluate\npharmacokinetics, drug-likeness and medicinal chemistry friendliness\nof small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"2026083119145408100_cit41","doi-asserted-by":"publisher","first-page":"W422","DOI":"10.1093\/nar\/gkae236","article-title":"ADMETlab 3.0:\nan updated comprehensive online ADMET prediction platform enhanced\nwith broader coverage, improved performance, API functionality and\ndecision support","volume":"52","author":"Fu","year":"2024","journal-title":"Nucleic Acids Res."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c04719","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/49881\/66534279\/acsomega.6c04719.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/49881\/66534279\/acsomega.6c04719.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:14:57Z","timestamp":1788218097000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/33\/49881\/5254733\/Design-Synthesis-and-Biological-Evaluation-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":41,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,13]]},"published-print":{"date-parts":[[2026,8,25]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c04719","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}