{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:12:54Z","timestamp":1792498374258,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Delivering carboxylic acid functions into cells is challenging due to their poor permeability across lipophilic membranes at physiological pH, where they are ionized. Masking carboxylic acids as esters improves cell entry, but once inside the cell, its rapid release is essential to maintain spatiotemporal control which can be beneficial for therapeutic and diagnostic applications. This study evaluates the 2\u2010hydroxyethyl\u2010dithio\u2010benzyl ester functional group which undergoes selective and rapid cleavage of the disulfide bond by thioredoxin (Trx), triggering rapid self\u2010immolation of the thio\u2010benzyl ester releasing the carboxylic acid. Fluorescence\u2010based assays using the pro\u2010fluorescent BODIPY structure have demonstrated the rapid intracellular release of carboxylic acids within minutes in both eukaryotic and prokaryotic cells. The approach was tested on antibiotics, and among them, levofloxacin ester prodrug, having the 2\u2010hydroxyethyl\u2010dithio\u2010benzyl ester functional group, showed significantly enhanced antimicrobial activity against resistant and intracellular bacteria compared to its methyl ester analogue.<\/jats:p>","DOI":"10.1002\/cmdc.202500056","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T07:26:06Z","timestamp":1739777166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fast Release of Carboxylic Acid inside Cells"],"prefix":"10.1002","volume":"20","author":[{"given":"Pascal","family":"Moser","sequence":"first","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Zelli","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro J.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"},{"name":"Univ. Federal de Vi\u04abosa UFV-CAF  35690000 Florestal Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micka\u00ebl","family":"Henry","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Sanchez\u2010Garcia","sequence":"additional","affiliation":[{"name":"Laboratoire de Bact\u00e9riologie-Hygi\u00e8ne Hospitali\u00e8re CHU Grenoble Alpes  CS10317 38043 Grenoble cedex 9 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Caspar","sequence":"additional","affiliation":[{"name":"Laboratoire de Bact\u00e9riologie-Hygi\u00e8ne Hospitali\u00e8re CHU Grenoble Alpes  CS10317 38043 Grenoble cedex 9 France"},{"name":"Univ. Grenoble Alpes CNRS CEA IBS Bact.Path. &amp; Cel. Resp.  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian C.","family":"Marro","sequence":"additional","affiliation":[{"name":"Biozentrum University of Basel  Basel 4056 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Chovelon","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaione","family":"Saez Cabodevilla","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"},{"name":"Univ. Grenoble Alpes CEA CNRS LCBM, UMR 5249  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine Ollagnier","family":"de Choudens","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CEA CNRS LCBM, UMR 5249  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Faudry","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS CEA IBS Bact.Path. &amp; Cel. Resp.  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-9681","authenticated-orcid":false,"given":"Yung\u2010Sing","family":"Wong","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes CNRS DPM  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cptc.202000253"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.9b00711"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201900098"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.2c01873"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.8b00371"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00894"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.4c00446"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.6b00405"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.202300100"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.8b00887"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.6b00324"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CC03336A"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b01779"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201500088"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00431"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b11302"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0SC00929F"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c03234"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c01213"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04035-y"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202110495"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201501127"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201303868"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/marc.201900531"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9MD00120D"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13664"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500056","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T17:49:40Z","timestamp":1760291380000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,5,5]]}},"alternative-id":["10.1002\/cmdc.202500056"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500056","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,17]]},"assertion":[{"value":"2025-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500056"}}