{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:29:45Z","timestamp":1788492585443,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Taxanes and other tubulin\u2010targeting medications are essential for treating advanced malignancies, especially in patients undergoing less aggressive chemotherapy. However, their clinical efficacy is often limited by significant off\u2010target toxicity and adverse side effects. In this study, the synthesis and characterisation of novel steroidal A\u2010ring\u2010fused isoxazoles, which were obtained through iodine\u2010mediated oxidative cyclization of dihydrotestosterone (DHT)\u2010derived \u03b1,\u03b2\u2010unsaturated oximes, are reported. According to mechanistic studies, the most potent compounds induced mitotic arrest and disrupted cytoskeletal integrity at low micromolar concentrations. The lead compound,\n                    <jats:bold>2j<\/jats:bold>\n                    , notably increased the rate of tubulin polymerisation in vitro and stabilised polymerised tubulin in the cells, leading to a G2\/M block of the cell cycle. Molecular docking studies indicated that\n                    <jats:bold>2j<\/jats:bold>\n                    is bound preferably to the taxane site on tubulin, forming conserved interactions. MicroScale Thermophoresis was used to further study this binding and showed a nanomolar\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>D<\/jats:sub>\n                    for\n                    <jats:bold>2j<\/jats:bold>\n                    . The fact that\n                    <jats:bold>2j<\/jats:bold>\n                    maintained its activity in docetaxel\u2010resistant prostate cancer cells, demonstrating its ability to circumvent resistance pathways linked to existing therapies with taxane\u2010like drugs, supports its clinical relevance. Therefore, our results encourage additional research and development for its potential therapeutic use in cancer treatment, particularly in resistant cases.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70031","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T06:26:01Z","timestamp":1753338361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Isoxazole\u2010Based Compounds Targeting the Taxane\u2010Binding Site of Tubulin"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-8688","authenticated-orcid":false,"given":"Miroslav","family":"Pe\u0159ina","sequence":"first","affiliation":[{"name":"Department of Experimental Biology, Faculty of Science Palack\u00fd University Olomouc Olomouc Czech 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Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-7087","authenticated-orcid":false,"given":"Denisa","family":"Vesel\u00e1","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Science Palack\u00fd University Olomouc Olomouc Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9685-813X","authenticated-orcid":false,"given":"Ren\u00e1ta","family":"Minorics","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy University of Szeged Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-5300","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Zupko","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy University of Szeged Szeged 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