{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:57:10Z","timestamp":1790567830077,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004702","name":"University of Genoa","doi-asserted-by":"publisher","award":["FRA 2024"],"award-info":[{"award-number":["FRA 2024"]}],"id":[{"id":"10.13039\/501100004702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministry for Universities and Research","doi-asserted-by":"publisher","award":["#2022P9RM9M"],"award-info":[{"award-number":["#2022P9RM9M"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["Ricerca corrente 2025"],"award-info":[{"award-number":["Ricerca corrente 2025"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>\n                    A series of pyrazolyl\u2010thioureas was designed and synthesized as novel sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) inhibitors. Compounds were prepared through a multistep, divergent procedure starting from amino pyrazole intermediates. Biological evaluation revealed that several derivatives exhibited significant SIRT2 inhibitory activity, with compounds\n                    <jats:bold>6a<\/jats:bold>\n                    and\n                    <jats:bold>7f<\/jats:bold>\n                    emerging as the most promising inhibitors, showing IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 2.2 and 13.6\u2009\u00b5M, respectively. Selected compounds displayed selective antiproliferative activity against HepG2 hepatocellular carcinoma cells, while showing limited cytotoxicity toward normal fibroblasts. The biological properties of\n                    <jats:bold>6a<\/jats:bold>\n                    and\n                    <jats:bold>7f<\/jats:bold>\n                    were further investigated by analyzing SIRT1 activity and correlating antiproliferative activity with tubulin acetylation. Docking simulations identified the molecular basis of SIRT1 and SIRT2 inhibition. Overall, these results identify pyrazolyl thioureas as a promising scaffold for novel SIRT1 and SIRT2 inhibitors with potential anticancer applications.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70489","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:15:23Z","timestamp":1790216123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Biological Evaluation of Pyrazolyl Thioureas (PTUs) as SIRT1 and SIRT2 Inhibitors"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-7891","authenticated-orcid":false,"given":"Matteo","family":"Lusardi","sequence":"first","affiliation":[{"name":"Department of Pharmacy Universit\u00e0 degli Studi di Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Astigiano","sequence":"additional","affiliation":[{"name":"Department of 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