{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:54:54Z","timestamp":1773035694945,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministry of Education, University and Research","doi-asserted-by":"publisher","award":["352\/2022"],"award-info":[{"award-number":["352\/2022"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002446","name":"CUP","doi-asserted-by":"publisher","award":["J44D22000960009"],"award-info":[{"award-number":["J44D22000960009"]}],"id":[{"id":"10.13039\/501100002446","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":[[2026,2,25]]},"abstract":"<jats:p>\n                    Human elastase 1 has been shown to possess an important role in maintaining skin stability and elasticity through the proteolytic cleavage of elastin (ELN), a hydrophobic protein that serves as a key component of extracellular matrix in the skin. The development of antielastase agents represents a promising therapeutic approach for treating skin pathologies characterized by elastin degradation, with applications in both dermatology and cosmetology. Reversible inhibitors represent a therapeutic strategy, offering selective inhibition of elastase proteolytic activity while preserving the function of other physiologically essential serine proteases. Using porcine pancreatic elastase (PPE) as a well\u2010established surrogate of human skin elastase, a focused series of noncovalent inhibitors designed to bind the catalytic area of PPE is assayed. Several compounds display an antielastase activity, including\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2\u2010bromophenyl)\u20102\u2010(6\u2010chloro\u20101\u2010(3,5\u2010dimethylbenzyl)\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010benzo[d]imidazol\u20102\u2010ylthio)acetamide (\n                    <jats:bold>7<\/jats:bold>\n                    ) that exhibits the most potent inhibitory effects (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200941.1\u2009\u00b5M), similar to standard compound oleanolic acid (IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 25.7\u2009\u00b5M). The observed structure\u2013activity relationship is further validated through molecular docking and dynamic studies, which provide mechanistic understanding of the binding interactions and establish suggestions for further rational drug design.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500879","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:25:38Z","timestamp":1766363138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Ligand\u2010Binding Properties of N\u2010arylbenzimidazoles as Novel Elastase Inhibitors"],"prefix":"10.1002","volume":"21","author":[{"given":"Giovanna","family":"Pitasi","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale F. Stagno D\u2019Alcontres 31 I\u201098125 Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Floris","sequence":"additional","affiliation":[{"name":"Department of Life and Environment Sciences University of Cagliari  I\u201009042 Monserrato Cagliari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale F. Stagno D\u2019Alcontres 31 I\u201098125 Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Savoca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Viale F. 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