{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:56:16Z","timestamp":1775832976918,"version":"3.50.1"},"reference-count":38,"publisher":"Cambridge University Press (CUP)","issue":"5","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Leishmania<\/jats:italic> is a trypanosomatid parasite that causes skin lesions in its cutaneous form. Current therapies rely on old and expensive drugs, against which the parasites have acquired considerable resistance. Trypanosomatids are unable to synthesize purines relying on salvaging from the host, and nucleoside analogues have emerged as attractive antiparasitic drug candidates. 4-Methyl-7-\u03b2-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidine (CL5564), an analogue of tubercidin in which the amine has been replaced by a methyl group, demonstrates activity against <jats:italic>Trypanosoma cruzi<\/jats:italic> and <jats:italic>Leishmania infantum<\/jats:italic>. Herein, we investigated its <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> activity against <jats:italic>L. amazonensis<\/jats:italic>. CL5564 was 6.5-fold (<jats:italic>P<\/jats:italic> = 0.0002) more potent than milteforan\u2122 (ML) against intracellular forms in peritoneal mouse macrophages, and highly selective, while combination with ML gave an additive effect. These results stimulated us to study the activity of CL5564 in mouse model of cutaneous Leishmania infection. BALB\/c female and male mice infected by <jats:italic>L. amazonensis<\/jats:italic> treated with CL5564 (10 mg kg<jats:sup>\u22121<\/jats:sup>, intralesional route for five days) presented a &gt;93% reduction of paw lesion size likely ML given orally at 40 mg kg<jats:sup>\u22121<\/jats:sup>, while the combination (10 + 40 mg kg<jats:sup>\u22121<\/jats:sup> of CL5564 and ML, respectively) caused &gt;96% reduction. The qPCR confirmed the suppression of parasite load, but only the combination approach reached 66% of parasitological cure. These results support additional studies with nucleoside derivatives.<\/jats:p>","DOI":"10.1017\/s0031182024000362","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T08:22:36Z","timestamp":1711527756000},"page":"506-513","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":6,"title":["N<sup>6<\/sup>-methyltubercidin gives sterile cure in a cutaneous <i>Leishmania amazonensis<\/i> mouse model"],"prefix":"10.1017","volume":"151","author":[{"given":"Cassandra","family":"Present","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberson 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