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In this work we tested a class of 15 quinolinylhydrazone analogues and presented data that support the use of the most active compound in cutaneous leishmaniasis caused by <jats:italic>Leishmania amazonensis<\/jats:italic>. In general, the compounds showed activity at low concentrations for both parasitic forms (5.33\u201337.04\u2009\u03bcM to promastigotes, and 14.31\u201361.98\u2009\u03bcM to amastigotes). In addition, the best compound (<jats:bold>MHZ15<\/jats:bold>) is highly selective for the parasite. Biochemical studies indicate that the treatment of promastigotes with <jats:bold>MHZ15<\/jats:bold> leads the loss of mitochondrial potential and increase in ROS levels as the primary effects, which triggers accumulation of lipid droplets, loss of plasma membrane integrity and apoptosis hallmarks, including DNA fragmentation and phosphatidylserine exposure. These effects were similar in the intracellular form of the parasite. However, in this parasitic form there is no change in plasma membrane integrity in the observed treatment time, which can be attributed to metabolic differences and the resilience of the amastigote. Also, ultrastructural changes such as vacuolization suggesting autophagy were observed. The in\u00a0vivo effectiveness of <jats:bold>MHZ15<\/jats:bold> in the experimental model of cutaneous leishmaniasis was carried out in mice of the BALB\/c strain infected with <jats:italic>L<\/jats:italic>. <jats:italic>amazonensis<\/jats:italic>. The treatment by intralesional route showed that <jats:bold>MHZ15<\/jats:bold> acted with great efficiency with significantly reduction in the parasite load in the injured paws and draining lymph nodes, without clinical signs of distress or compromise of animal welfare. In\u00a0vivo toxicity was also evaluated and null alterations in the levels of hepatic enzymes aspartate aminotransferase, and alanine aminotransferase was observed. The data presented herein demonstrates that <jats:bold>MHZ15<\/jats:bold> exhibits a range of favorable characteristics conducive to the development of an antileishmanial agent.<\/jats:p>","DOI":"10.1111\/cbdd.14535","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T02:24:47Z","timestamp":1716344687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["4\u2010Quinolinylhydrazone analogues kill <i>Leishmania (Leishmania) amazonensis<\/i> by inducing apoptosis and mitochondria\u2010dependent pathway cell death"],"prefix":"10.1111","volume":"103","author":[{"given":"Juliana da Trindade","family":"Granato","sequence":"first","affiliation":[{"name":"Departamento de Parasitologia, Microbiologia e Imunologia Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Juiz de Fora  Juiz de Fora Minas Gerais 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Valle","family":"Midlej","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz)  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Maria Ribeiro","family":"Antinarelli","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Microbiologia e Imunologia Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Juiz de Fora  Juiz de Fora Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo Firmino da","family":"Silva\u00a0Neto","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Medicina Universidade Federal de Juiz de Fora  Juiz de Fora Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vin\u00edcius 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