{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T23:23:26Z","timestamp":1767914606538,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programma Ricerca di Ateneo UNICT 2020-2022 linea 2","award":["Project number 57722172126;"],"award-info":[{"award-number":["Project number 57722172126;"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Novel heme oxygenase-1 (HO-1) inducers based on dimethyl fumarate (DMF) structure are reported in this paper. These compounds are obtained by modification of the DMF backbone. Particularly, maintaining the \u03b1, \u03b2-unsaturated dicarbonyl function as the central chain crucial for HO-1 induction, different substituted or unsubstituted phenyl rings are introduced by means of an ester or amide linkage. Symmetric and asymmetric derivatives are synthesized. All compounds are tested on a human hepatic stellate cell line LX-2 to assay their capacity for modifying HO-1 expression. Compounds 1b, 1l and 1m stand out for their potency as HO-1 inducers, being 2\u20133 fold more active than DMF, and for their ability to reverse reactive oxygen species (ROS) production mediated using palmitic acid (PA). These properties, coupled with a low toxicity toward LX-2 cell lines, make these compounds potentially useful for treatment of diseases in which HO-1 overexpression may counteract inflammation, such as hepatic fibrosis. Docking studies show a correlation between predicted binding free energy and experimental HO-1 expression data. These preliminary results may support the development of new approaches in the management of liver fibrosis.<\/jats:p>","DOI":"10.3390\/ijms21249541","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T09:12:57Z","timestamp":1608023577000},"page":"9541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel Heme Oxygenase-1 (HO-1) Inducers Based on Dimethyl Fumarate Structure"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-1495","authenticated-orcid":false,"given":"Valeria","family":"Sorrenti","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6314-6029","authenticated-orcid":false,"given":"Luca","family":"Vanella","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara Bianca Maria","family":"Platania","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-7070","authenticated-orcid":false,"given":"Khaled","family":"Greish","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Bucolo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-0308","authenticated-orcid":false,"given":"Valeria","family":"Pittal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0162-0134(00)00156-2","article-title":"Mechanism of heme degradation by heme oxygenase","volume":"82","author":"Yoshida","year":"2000","journal-title":"J. Inorg. Bochem."},{"key":"ref_2","first-page":"797","article-title":"The heme oxygenase system: Past, present, and future","volume":"6","author":"Maines","year":"2004","journal-title":"Antioxid. 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