{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:27:48Z","timestamp":1787063268226,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>\n                    Cancer remains one of the leading causes of mortality, accounting for millions of deaths worldwide each year and posing a persistent challenge to global health despite advances in diagnosis and treatment. Dual inhibition of thioredoxin reductase (TrxR) and cancer\u2010associated carbonic anhydrase (CA) isoforms IX and XII represents a promising strategy for selective anticancer therapy by simultaneously disrupting cellular redox homeostasis and pH regulation. The antibacterial agent furagin has been previously explored as an inhibitor of cancer\u2010associated carbonic anhydrases; however, its potential as a TrxR inhibitor has not yet been investigated. In this study, a series of furagin derivatives\u2014nitrofuran\u2010based hydrazones (\n                    <jats:bold>7a<\/jats:bold>\n                    \u2013\n                    <jats:bold>7s<\/jats:bold>\n                    )\u2014were designed and synthesized as potential dual TrxR\/CA inhibitors. The derivatives were screened for CA inhibition using a stopped\u2010flow CO\n                    <jats:sub>2<\/jats:sub>\n                    hydration assay and for rTrxR1 inhibition via a 5,5\u2032\u2010Dithiobis(2\u2010nitrobenzoic acid) (DTNB) reduction assay. Most derivatives displayed weak or negligible activity against the cytosolic isoforms hCA I and hCA II while exhibiting moderate and selective inhibition of the cancer\u2010associated isoforms hCA IX and hCA XII, particularly hCA XII. Several compounds also inhibited rTrxR1, with compound\n                    <jats:bold>7g<\/jats:bold>\n                    emerging as the most potent inhibitor in the series (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200911\u2009\u03bcM).\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70379","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:30:09Z","timestamp":1783567809000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Furagin Derivatives\u2014Nitrofuran\u2010Based Hydrazones as Potential Dual Inhibitors of Thioredoxin Reductase and Carbonic Anhydrases"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-7372","authenticated-orcid":false,"given":"Aleksandrs","family":"Pustenko","sequence":"first","affiliation":[{"name":"Latvian Institute of Organic Synthesis  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raitis","family":"Bobrovs","sequence":"additional","affiliation":[{"name":"The National Institute of Research and Innovation (NIRI)  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katr\u012bna","family":"Freimane","sequence":"additional","affiliation":[{"name":"The National Institute of Research and Innovation (NIRI)  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antons","family":"Sizovs","sequence":"additional","affiliation":[{"name":"The National Institute of Research and Innovation (NIRI)  Riga Latvia"},{"name":"Baltic Biomaterials Centre of Excellence Headquarters at Riga Technical University  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-7192","authenticated-orcid":false,"given":"Andrea","family":"Angeli","sequence":"additional","affiliation":[{"name":"Department of Neurofarba Universit\u00e0 degli Studi di Firenze  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Department of Neurofarba Universit\u00e0 degli Studi di Firenze  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raivis","family":"\u017dalubovskis","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis  Riga Latvia"},{"name":"Institute of Chemistry and Chemical Technology Faculty of Natural Sciences and Technology Riga Technical University  Riga 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