Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity

PLoS One. 2022 Jun 6;17(6):e0269447. doi: 10.1371/journal.pone.0269447. eCollection 2022.


Leishmaniasis is a public health issue. 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 in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in -vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents* / pharmacokinetics
  • Antiprotozoal Agents* / therapeutic use
  • Leishmania major*
  • Leishmaniasis, Cutaneous* / drug therapy
  • Mammals
  • Mice
  • Mice, Inbred BALB C
  • Neglected Diseases / drug therapy


  • Antiprotozoal Agents

Grant support

The project received the following funding for its realization: CNPQ (Conselho Nacional de Desenvolvimento Científico e Tecnológico) Process#465.249/2014-0; FAPERJ (Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro) Process#E-26/010.000090/2018 and E-26/202.676/2019; FAPEAL (Fundação de amparo a pesquisa do estado de Alagoas); INCT-INOFAR (Instituto Nacional de Ciência e Tecnologia em Fármacos e Medicamentos) Process: 465.249/2014-0 and E-26/010.000090/2018; CAPES (coordenação de aperfeiçoamento de pessoal de nível superior), process#001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.