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It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the<jats:italic>in vitro<\/jats:italic>pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low<jats:italic>in vitro<\/jats:italic>systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. It exhibited no cytotoxic effect to mammalian cells and displayed good<jats:italic>in \u2013vivo<\/jats:italic>effect against BALB\/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.<\/jats:p>","DOI":"10.1371\/journal.pone.0269447","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T17:24:20Z","timestamp":1654536260000},"page":"e0269447","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-2726","authenticated-orcid":true,"given":"Aline Cavalcanti","family":"de Queiroz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-2627","authenticated-orcid":true,"given":"Gisele","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vict\u00f3ria Regina Thomaz","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lio","family":"de Mattos Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Amaral","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Carregaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Santana da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliezer Jesus","family":"Barreiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magna Suzana","family":"Alexandre-Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-6351","authenticated-orcid":true,"given":"Lidia Moreira","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"pone.0269447.ref001","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: a review","volume":"6","author":"E Torres-Guerrero","year":"2017","journal-title":"F1000Res"},{"key":"pone.0269447.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2016.11.012","article-title":"Leishmania infections: Molecular targets and diagnosis","volume":"57","author":"M Akhoundi","year":"2017","journal-title":"Molecular Aspects of Medicine"},{"key":"pone.0269447.ref003","unstructured":"World Health Organization. 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