{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:45Z","timestamp":1791438885367,"version":"4.3.3"},"reference-count":54,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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":[[2026,8,14]]},"abstract":"<jats:p>\n                    Neurodegenerative diseases\u2019 treatments still represent one of the major unmet medical needs, and their related clinical trials are characterized by one of the highest failure rates. Despite the promising preclinical premises, pioglitazone lies among those drugs that failed clinical translation. It is an antidiabetic drug acting as a PPAR\u03b3 agonist and later repurposed as a competitive and selective MAO\u2010B inhibitor featuring polyhedral neuroprotective properties. In pursuing our efforts to broaden the therapeutic potential of pioglitazone toward the neurodegenerative context, we herein developed and preliminarily characterized a new series of glitazone derivatives. Particularly, by means of different connectors, a disulfide covalent warhead was attached to the 5\u2010benzylthiazolidine\u20102,4\u2010dione head to potentially engage cysteines located in MAO\u2010B and PPAR\u03b3 binding sites and turn pioglitazone into a prolonged\u2010acting modulator. Interestingly, compound\n                    <jats:bold>5<\/jats:bold>\n                    emerged as a selective competitive MAO\u2010B inhibitor and a PPAR\u03b3 agonist with a very slow dissociation rate, revealing long\u2010lasting target engagement, albeit exhibiting lower potencies with respect to pioglitazone. This peculiar biological profile resulted in promising antioxidant and anti\u2010inflammatory properties, laying the ground for future development of covalent pioglitazone derivatives.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70405","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:38:26Z","timestamp":1785379106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Disulfide Bridge as a Tool to Improve Pioglitazone\u2019s Neuroprotective Potential: Toward the Development of Prolonged\u2010Acting MAO\u2010B\/PPAR\u03b3 Modulators"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0710-4251","authenticated-orcid":false,"given":"Filippo","family":"Basagni","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Biotechnology Alma Mater Studiorum\u2010University of Bologna  Bologna 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