{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:17:28Z","timestamp":1788545848509,"version":"build-2803163510"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"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","award":["E-26\/202 421\/2017"],"award-info":[{"award-number":["E-26\/202 421\/2017"]}],"id":[{"id":"10.13039\/501100004586","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","award":["E-26\/201.905\/2020"],"award-info":[{"award-number":["E-26\/201.905\/2020"]}],"id":[{"id":"10.13039\/501100004586","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","award":["E-26\/202.942\/2019"],"award-info":[{"award-number":["E-26\/202.942\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["PQ-2 (304712\/2016-7)"],"award-info":[{"award-number":["PQ-2 (304712\/2016-7)"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Current treatment available for leishmaniasis is fraught with numerous problems, so the search for new treatment alternatives for leishmaniasis is urgent and necessary. The proteasome has been selected as a promising target. Marizomib is a proteasome inhibitor and has shown antitumor effects, with ongoing clinical tests. In this work, we aimed to evaluate the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      effects of Marizomib on\n                      <jats:italic toggle=\"yes\">Leishmania amazonensis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Leishmania infantum<\/jats:italic>\n                      . Interestingly, Marizomib was not effective against promastigote forms of\n                      <jats:italic toggle=\"yes\">L. amazonensis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">L. infantum in vitro<\/jats:italic>\n                      but showed a significant effect against intracellular amastigotes of\n                      <jats:italic toggle=\"yes\">L. amazonensis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">L. infantum<\/jats:italic>\n                      , showing selectivity for the parasite when compared to the host cell. Furthermore, through transmission electron microscopy, it was possible to show that Marizomib induces extensive ultrastructural changes in amastigotes of\n                      <jats:italic toggle=\"yes\">L. amazonensis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">L. infantum<\/jats:italic>\n                      , such as the appearance of many vacuoles in the parasite cytoplasm and mitochondrial swelling. Marizomib was also shown to be effective in a murine model of cutaneous leishmaniasis, with a reduction in the size of lesions and parasite load in the footpads and draining lymph nodes of animals infected with\n                      <jats:italic toggle=\"yes\">L. amazonensis<\/jats:italic>\n                      . It is also effective in a model of visceral leishmaniasis, with a reduction in parasite load in the spleen and liver of animals infected with\n                      <jats:italic toggle=\"yes\">L. infantum<\/jats:italic>\n                      . Importantly, Marizomib, in the treatment regimens used, did not cause renal and hepatic acute toxicity to infected animals. These results highlight the antileishmanial potential of Marizomib, encouraging us to conduct preclinical tests in other animal models, as well as clinical trials.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00286-25","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T13:40:37Z","timestamp":1753105237000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    antileishmanial potential of Marizomib against\n                    <i>Leishmania amazonensis<\/i>\n                    and\n                    <i>Leishmania infantum<\/i>"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4223-3690","authenticated-orcid":false,"given":"Patr\u00edcia de Almeida","family":"Machado","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02rjhbb08","id-type":"ROR","asserted-by":"publisher"}],"name":"Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense","place":["Niter\u00f3i, Brazil"]},{"id":[{"id":"https:\/\/ror.org\/04jhswv08","id-type":"ROR","asserted-by":"publisher"}],"name":"Laborat\u00f3rio de Imunologia Cl\u00ednica, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz-Fiocruz","place":["Rio de Janeiro, Brazil"]},{"id":[{"id":"https:\/\/ror.org\/03490as77","id-type":"ROR","asserted-by":"publisher"}],"name":"Laborat\u00f3rio de Imunobiotecnologia, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]},{"id":[{"id":"https:\/\/ror.org\/04yqw9c44","id-type":"ROR","asserted-by":"publisher"}],"name":"N\u00facleo de Pesquisas em Parasitologia (NUPEP), Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Juiz de 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