{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T10:05:09Z","timestamp":1763028309315,"version":"3.45.0"},"reference-count":34,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PNRR \u201cTHE\u2014Tuscany Health Ecosystem\u201d","award":["ECS00000017\u2014CUP I53C22000780001"],"award-info":[{"award-number":["ECS00000017\u2014CUP I53C22000780001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase implicated in various physiological and pathological processes, including cardiovascular diseases. The lead compound for SIRT1, resveratrol (1), as well as natural-derived and synthetic SIRT1-activating compounds demonstrated to exert cardioprotective effects. In the present work, we evaluated a small series of diarylimidazoles, of which 4 emerged, in in vitro enzymatic assays, as an activator of SIRT1 endowed with a similar potency compared with that of 1. Therefore, 4 was subjected to pharmacological investigation, where it was proven to reduce myocardial damage induced by ischemia\/reperfusion injury in isolated rat hearts, thus demonstrating its cardioprotective properties. An in silico study suggested the binding mode of this derivative within SIRT1 in the presence of the p53-AMC-peptide. These promising results could pave the way to further expand and optimize this chemical class of new SIRT1 activators as potential cardioprotective agents.<\/jats:p>","DOI":"10.3390\/molecules30224378","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:59:09Z","timestamp":1763027949000},"page":"4378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Investigation of a Novel Resveratrol-like SIRT1 Activator Endowed with a Cardioprotective Profile"],"prefix":"10.3390","volume":"30","author":[{"given":"Leonardo","family":"Carbonetti","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno, I-56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-6242","authenticated-orcid":false,"given":"Simone","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno, I-56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5408-9416","authenticated-orcid":false,"given":"Rosarita","family":"D\u2019Orsi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry, University of Pisa, Via Giuseppe Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0090-7070","authenticated-orcid":false,"given":"Marco","family":"Lessi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry, University of Pisa, Via Giuseppe Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno, I-56126 Pisa, Italy"},{"name":"Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Via Risorgimento 36, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-6248","authenticated-orcid":false,"given":"Lara","family":"Testai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno, I-56126 Pisa, Italy"},{"name":"Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Via Risorgimento 36, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-7008","authenticated-orcid":false,"given":"Fabio","family":"Bellina","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry, University of Pisa, Via Giuseppe Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105930","DOI":"10.1016\/j.ejps.2021.105930","article-title":"Identification of novel SIRT1 activators endowed with cardioprotective profile","volume":"165","author":"Flori","year":"2021","journal-title":"Eur. 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