{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:10:31Z","timestamp":1790759431088,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202006995003"],"award-info":[{"award-number":["202006995003"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","award":["BOF20\/IOP\/006"],"award-info":[{"award-number":["BOF20\/IOP\/006"]}],"id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007229","name":"Bijzonder Onderzoeksfonds UGent","doi-asserted-by":"publisher","award":["BOF.BAS.2020.0035.01"],"award-info":[{"award-number":["BOF.BAS.2020.0035.01"]}],"id":[{"id":"10.13039\/501100007229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["FWO\u2010WEAVE G000123N"],"award-info":[{"award-number":["FWO\u2010WEAVE G000123N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S05525N"],"award-info":[{"award-number":["1S05525N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Curcumin, a natural polyphenol with anti\u2010cancer potential, faces limitations due to metabolic instability, and non\u2010specific toxicity. This study focused on four curcumin analogs (FM038, FM044, FM045, FM050) featuring oxobutenylidene\u2010substituted benzothiazepane cores bearing pyridinyl or furan substituents. We systematically evaluated their selective toxic effect on human colon (Caco\u20102) and liver (HepG2) cells. This study reveals that structural modifications critically govern the selective cytotoxicity of curcumin analogs towards proliferating Caco\u20102 and HepG2 cells. Treatment with analogs featuring pyridin\u20102\u2010yl substituents (FM045\/FM050) resulted in a slightly reduced potency towards Caco\u20102 cells compared to curcumin, whereas FM044 (furan\u20102\u2010yl) was non\u2010toxic and FM038 (pyridin\u20103\u2010yl, methylated core) maintained similar activity. In contrast, direct exposure to proliferating HepG2 cells resulted in less cytotoxicity compared to the Caco\u20102 cell line, which points to a cell\u2010specific mode\u2010of\u2010action in growing cells. When combined in a co\u2010culture, metabolites generated and\/or transported by differentiated Caco\u20102 cells significantly decreased HepG2 viability at an apical concentration of 15\u2009\u03bcM. Efflux analysis of respiration and acidification showed that FM050 induced the strongest mitochondrial dysfunction in Caco\u20102 cells, directly driving cytotoxicity, whereas HepG2 toxicity correlated with intrinsic detoxification capacity rather than mitochondrial disruption. A metabolic shift towards glycolysis was observed in both cell lines, indicating energy pathway modulation to a more dysfunctional phenotype. These findings highlight the dual role of structural optimization (e.g., methylation, heterocyclic substituents) for (cancer) cell\u2010specific bioactivity and colonic metabolism and may guide future development of curcumin\u2010based chemopreventive agents after in\u00a0vivo validation and metabolite characterization.<\/jats:p>","DOI":"10.1111\/cbdd.70406","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:06:41Z","timestamp":1790053601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Benzothiazepane\u2010Based Curcumin Analogs Show Selective Effects on Respiration, Permeability, and Growth of Gut\u2010Liver (Co\u2010Culture) Cell Models"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1021-2002","authenticated-orcid":false,"given":"Fuhua","family":"Li","sequence":"first","affiliation":[{"name":"College of Food Science Southwest University  Chongqing People's Republic of China"},{"name":"Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-5950","authenticated-orcid":false,"given":"Julie","family":"De Munck","sequence":"additional","affiliation":[{"name":"Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2040-2318","authenticated-orcid":false,"given":"Felien","family":"Morlion","sequence":"additional","affiliation":[{"name":"SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-5311","authenticated-orcid":false,"given":"Katarina","family":"Magdalenic","sequence":"additional","affiliation":[{"name":"SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-0564","authenticated-orcid":false,"given":"Andreja","family":"Rajkovic","sequence":"additional","affiliation":[{"name":"Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4442-4337","authenticated-orcid":false,"given":"Matthias","family":"D'hooghe","sequence":"additional","affiliation":[{"name":"SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-6107","authenticated-orcid":false,"given":"John","family":"Van Camp","sequence":"additional","affiliation":[{"name":"Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-135X","authenticated-orcid":false,"given":"Charlotte","family":"Grootaert","sequence":"additional","affiliation":[{"name":"Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2019.05.022"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.140815"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.31015\/2025.2.29"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.26650\/IstanbulJPharm.2020.0039"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010019\u20100173\u20108"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574892810666151020101706"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.06.006"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23136945"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521\u20101878"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.inoche.2021.108482"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4745252"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmd.2026.100376"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.1030936"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn064"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17020189"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155541"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010022\u201004311\u20104"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11694\u2010025\u201003392\u20106"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1np00051a"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119897"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2007.02.014"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.004044"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.116034"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/sca.21058"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557521666210122153823"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134054"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2007.02.014"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.10.007"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13621"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2014.11.090"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/87559129.2024.2360539"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.12.001"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072138"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2005.10.010"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2024.133884"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101791"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234386"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28122"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00975"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20103495(99)77363\u20107"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105405"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh2771"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2022.135313"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113528"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570\u20109639(03)00204\u20108"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-821562-3.00050-2"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201081733\u20103"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14030611"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/mi12060685"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmd.2026.100376"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000132"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.11.055"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2025.156933"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15080950"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2017.04.004"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cofs.2016.02.002"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.02.002"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5570796"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70406","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.70406","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:54:11Z","timestamp":1790758451000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.70406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/cbdd.70406"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.70406","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70406"}}