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The therapeutic arsenal against these neglected tropical diseases is limited, and the emergence of resistance to available medicines complicates treatment. These kinetoplastid parasites share a unique DNA modification, that is \u03b2\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010glucosyl\u20105\u2010hydroxymethyluracil (base J), which appears to play an essential role in parasite development and survival through an original epigenetic mechanism, allowing adaptation to environmental changes. To date, the regulatory pathway of this unique nucleobase has not been explored as a potential therapeutic target. In this work, we report the synthesis of several families of base J analogues and assess their potential against different kinetoplastid species. Some compounds have shown antiparasitic activity and no toxicity toward human primary fibroblasts, revealing promising new strategies for antiparasitic therapy.\n                  <\/jats:p>","DOI":"10.1002\/chem.202503227","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T14:24:10Z","timestamp":1767882250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and Evaluation of the First Generation of Glycosylated Nucleoside Analogues as Potential Inhibitors of the Base J Metabolism in Kinetoplastid Parasites"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-7065","authenticated-orcid":false,"given":"Oc\u00e9ane","family":"Monfret","sequence":"first","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Louis","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihem","family":"Rebei","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-5386","authenticated-orcid":false,"given":"Dominique","family":"Urban","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6653-7685","authenticated-orcid":false,"given":"Yann","family":"Bourdreux","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Mouray","sequence":"additional","affiliation":[{"name":"MCAM, UMR 7245 CNRS Mus\u00e9um National d'Histoire Naturelle, CNRS, CP52, 57 rue Cuvier  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-0465","authenticated-orcid":false,"given":"Philippe","family":"Grellier","sequence":"additional","affiliation":[{"name":"MCAM, UMR 7245 CNRS Mus\u00e9um National d'Histoire Naturelle, CNRS, CP52, 57 rue Cuvier  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-1243","authenticated-orcid":false,"given":"Gilles","family":"Doisneau","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7722-370X","authenticated-orcid":false,"given":"Dominique","family":"Guianvarc'h","sequence":"additional","affiliation":[{"name":"UMR CNRS 8182 Universit\u00e9 Paris\u2010Saclay, CNRS Institut de Chimie Mol\u00e9culaire et des Mat\u00e9riaux d'Orsay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11120.1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16\u201084256"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2016.11.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1179\/2047773213Y.0000000105"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apjtm.2016.06.021"},{"key":"e_1_2_7_7_1","article-title":"Climate Change and Vector\u2010borne Diseases: A Regional Analysis","volume":"12","author":"Githeko A. 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