{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:46:44Z","timestamp":1792025204763,"version":"4.4.0"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton\u2013McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.<\/jats:p>","DOI":"10.3390\/molecules27031034","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T11:35:17Z","timestamp":1643974517000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unprecedented Epimerization of an Azithromycin Analogue: Synthesis, Structure and Biological Activity of 2\u2032-Dehydroxy-5\u2033-Epi-Azithromycin"],"prefix":"10.3390","volume":"27","author":[{"given":"Goran","family":"Kragol","sequence":"first","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Steadman","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zorica","family":"Maru\u0161i\u0107 I\u0161tuk","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8101-089X","authenticated-orcid":false,"given":"Ana","family":"\u010ciko\u0161","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Bosnar","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dubravko","family":"Jeli\u0107","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrijela","family":"Ergovi\u0107","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Trzun","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-7488","authenticated-orcid":false,"given":"Berislav","family":"Bo\u0161njak","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Bokuli\u0107","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasna","family":"Padovan","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Glojnari\u0107","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Erakovi\u0107 Haber","sequence":"additional","affiliation":[{"name":"Fidelta Ltd., Prilaz baruna Filipovi\u0107a 29, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.pharmthera.2014.03.003","article-title":"Azithromycin: Mechanisms of action and their relevance for clinical applications","volume":"143","author":"Parnham","year":"2014","journal-title":"Pharmacol. 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