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Treatment options are limited and toxicity exists, requiring an urgent search for new therapies.\n                      <jats:italic toggle=\"yes\">Leishmania<\/jats:italic>\n                      differs from mammalian cells by having unique mitochondria, which have been considered an important therapeutic target. Ubiquinone is found in the inner membrane of mitochondria and plays a critical role in the electron transport chain, which is essential for cell viability. The combination of buparvaquone and 4-nitrobenzoate seems an interesting option due to their action on these targets. The aim of the present work was to investigate the effects of this combination against\n                      <jats:italic toggle=\"yes\">Leishmania (Leishmania) amazonensis<\/jats:italic>\n                      infections\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      and to elucidate the possible mechanism of action of 4-nitrobenzoate. The results showed that the drug combination tested in promastigotes has an additive or indifferent effect. In the intracellular amastigotes, when buparvaquone was tested with fixed concentrations of 4-nitrobenzoate, concentrations that had no effect alone potentiated the effect of buparvaquone by two to four times. The mechanism of action of 4-nitrobenzoate in promastigote forms suggests a reduction in ubiquinone 6 levels, an alteration in mitochondrial membrane potential, and an increase in reactive oxygen species.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      treatment with a topical formulation (buparvaquone 0.1% and 4-nitrobenzoate 0.1%) in infected mice showed a reduction in parasite burden of 57% compared to the control group, suggesting that this combination may represent a promising therapeutic strategy for future treatment of this disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00824-25","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T13:19:26Z","timestamp":1759843166000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    study of the inhibition of ubiquinone biosynthesis in\n                    <i>Leishmania (Leishmania) amazonensis<\/i>\n                    using the combination of buparvaquone and 4-nitrobenzoate as a strategy for the discovery of new therapeutic targets"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-3400","authenticated-orcid":true,"given":"Juliana Tonini","family":"Mesquita","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Parasitology, Institute of Biomedical Sciences, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel C\u00e2ndido","family":"Moura","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Parasitology, 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