{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:13:49Z","timestamp":1771478029154,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}]},{"name":"Italian Ministry of University and Research","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}]},{"name":"FCT (Foundation for Science and Technology)","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}]},{"name":"FCT (Foundation for Science and Technology)","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}]},{"name":"Group of Natural Products and Medicinal Chemistry\u2014CIIMAR","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}]},{"name":"Group of Natural Products and Medicinal Chemistry\u2014CIIMAR","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural products have attracted attention due to their safety and potential effectiveness as anti-inflammatory drugs. Particularly, xanthones owning a unique 9H-xanthen-9-one scaffold, are endowed with a large diversity of medical applications, including antioxidant and anti-inflammatory activities, because their core accommodates a vast variety of substituents at different positions. Among others, \u03b1- and \u03b3-mangostin are the major known xanthones purified from Garcinia mangostana with demonstrated anti-inflammatory and antioxidant effects by in vitro and in vivo modulation of the Nrf2 (nuclear factor erythroid-derived 2-like 2) pathway. However, the main mechanism of action of xanthones and their derivatives is still only partially disclosed, and further investigations are needed to improve their potential clinical outcomes. In this light, a library of xanthone derivatives was synthesized and biologically evaluated in vitro on human macrophages under pro-inflammatory conditions. Furthermore, structure\u2013activity relationship (SAR) studies were performed by means of matched molecular pairs (MMPs). The data obtained revealed that the most promising compounds in terms of biocompatibility and counteraction of cytotoxicity are the ones that enhance the Nrf2 translocation, confirming a tight relationship between the xanthone scaffold and the Nrf2 activation as a sign of intracellular cell response towards oxidative stress and inflammation.<\/jats:p>","DOI":"10.3390\/ijms232113319","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T08:15:12Z","timestamp":1667376912000},"page":"13319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Natural and Synthetic Xanthone Derivatives Counteract Oxidative Stress via Nrf2 Modulation in Inflamed Human Macrophages"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2283-4159","authenticated-orcid":false,"given":"Marialucia","family":"Gallorini","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-9440","authenticated-orcid":false,"given":"Simone","family":"Carradori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-6060","authenticated-orcid":false,"given":"Diana I. S. P.","family":"Resende","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2013Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-8706","authenticated-orcid":false,"given":"Luciano","family":"Saso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cVittorio Erspamer\u201d, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9033-0104","authenticated-orcid":false,"given":"Alessia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-2143","authenticated-orcid":false,"given":"Andreia","family":"Palmeira","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2013Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"given":"Amelia","family":"Cataldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2013Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2013Interdisciplinary Centre of Marine and Environmental Research, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huang, Q., Wang, Y., Wu, H., Yuan, M., Zheng, C., and Xu, H. 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