{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:02:57Z","timestamp":1781877777392,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The synthesis and antiproliferative evaluation of novel <jats:sc>d<\/jats:sc>\u2010glucopyranuronamide\u2010containing nucleosides is described. Based on our previously reported anticancer <jats:sc>d<\/jats:sc>\u2010glucuronamide\u2010based nucleosides, new analogues comprising <jats:italic>N\/O<\/jats:italic>\u2010dodecyl or <jats:italic>N<\/jats:italic>\u2010propargyl substituents at the glucuronamide unit and anomerically\u2010N\u2010linked 2\u2010acetamido\u20106\u2010chloropurine, 6\u2010chloropurine or 4\u2010(6\u2010chloropurinyl)methyl triazole motifs were synthesized in 4\u20136 steps starting from acetonide\u2010protected glucofuranurono\u20106,3\u2010lactone. The methodologies were based on the access to <jats:italic>N<\/jats:italic>\u2010substituted glycopyranuronamide precursors, namely 1,2\u2010<jats:italic>O<\/jats:italic>\u2010acetyl derivatives or glucuronoamidyl azides for further nucleobase N\u2010glycosylation or 1,3\u2010dipolar cycloaddition with <jats:italic>N<\/jats:italic><jats:sup>9<\/jats:sup>\u2010 and <jats:italic>N<\/jats:italic><jats:sup>7<\/jats:sup>\u2010propargyl\u20106\u2010chloropurines, respectively. <jats:italic>N<\/jats:italic>\u2010Propargyl glucuronamide\u2010based N<jats:sup>9<\/jats:sup>\u2010purine nucleosides were converted into (triazolyl)methyl amide\u20106,6\u2010linked pseudodisaccharide nucleosides via cycloaddition with methyl 6\u2010azido\u2010glucopyranoside. A CuI\/Amberlyst A\u201021 catalytic system employed in the cycloaddition reactions also effected conversion into 6\u2010dimethylaminopurine nucleosides. Antiproliferative evaluation in chronic myeloid leukemia (K562) and breast cancer (MCF\u20107) cells revealed significant effects exhibited by the synthesized monododecylated purine\u2010containing nucleosides. A <jats:italic>N<\/jats:italic>\u2010propargyl 3\u2010<jats:italic>O<\/jats:italic>\u2010dodecyl glucuronamide derivative comprising a N<jats:sup>9<\/jats:sup>\u2010\u03b2\u2010linked 6\u2010chloropurine moiety was the most active compound against MCF\u20107 cells (GI<jats:sub>50<\/jats:sub>=11.9\u2005\u03bcM) while a related \u03b1\u2010(purinyl)methyltriazole nucleoside comprising a N<jats:sup>7<\/jats:sup>\u2010linked 6\u2010chloropurine moiety exhibited the highest activity against K562 cells (GI<jats:sub>50<\/jats:sub>=8.0\u2005\u03bcM). Flow cytometry and immunoblotting analysis of apoptosis\u2010related proteins in K562 cells treated with the <jats:italic>N<\/jats:italic>\u2010propargyl 3\u2010<jats:italic>O<\/jats:italic>\u2010dodecyl glucuronamide\u2010based N<jats:sup>9<\/jats:sup>\u2010linked 6\u2010chloropurine nucleoside indicated that it acts via apoptosis induction.<\/jats:p>","DOI":"10.1002\/cmdc.202300608","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T09:00:01Z","timestamp":1702544401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthesis and Antiproliferative Evaluation of <scp>d<\/scp>\u2010Glucuronamide\u2010Based Nucleosides and (Triazolyl)methyl Amide\u2010Linked Pseudodisaccharide Nucleosides**"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9205-138X","authenticated-orcid":false,"given":"T\u00e2nia","family":"Moreira","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias, Universidade de Lisboa  Ed. C8, 5\u00b0 Piso, Campo Grande 1749-016 Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingos M.","family":"Manuel","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias, Universidade de Lisboa  Ed. C8, 5\u00b0 Piso, Campo Grande 1749-016 Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Rosa","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias, Universidade de Lisboa  Ed. C8, 5\u00b0 Piso, Campo Grande 1749-016 Lisboa Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-0570","authenticated-orcid":false,"given":"Rafael Santana","family":"Nunes","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias, Universidade de Lisboa  Ed. C8, 5\u00b0 Piso, Campo Grande 1749-016 Lisboa Portugal"},{"name":"BioISI \u2013 Biosystems &amp; Integrative Sciences Institute Faculdade de Ci\u00eancias, Universidade de Lisboa  Ed. 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