Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity.
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 des...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0269447 |
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| author | Aline Cavalcanti de Queiroz Gisele Barbosa Victória Regina Thomaz de Oliveira Hélio de Mattos Alves Marina Amaral Alves Vanessa Carregaro João Santana da Silva Eliezer Jesus Barreiro Magna Suzana Alexandre-Moreira Lidia Moreira Lima |
| author_facet | Aline Cavalcanti de Queiroz Gisele Barbosa Victória Regina Thomaz de Oliveira Hélio de Mattos Alves Marina Amaral Alves Vanessa Carregaro João Santana da Silva Eliezer Jesus Barreiro Magna Suzana Alexandre-Moreira Lidia Moreira Lima |
| author_sort | Aline Cavalcanti de Queiroz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T00:47:45Z |
| format | Article |
| id | doaj.art-12b4110035ee4ff18acce1586f7c1e43 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T00:47:45Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-12b4110035ee4ff18acce1586f7c1e432022-12-22T00:44:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176e026944710.1371/journal.pone.0269447Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity.Aline Cavalcanti de QueirozGisele BarbosaVictória Regina Thomaz de OliveiraHélio de Mattos AlvesMarina Amaral AlvesVanessa CarregaroJoão Santana da SilvaEliezer Jesus BarreiroMagna Suzana Alexandre-MoreiraLidia Moreira LimaLeishmaniasis 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.https://doi.org/10.1371/journal.pone.0269447 |
| spellingShingle | Aline Cavalcanti de Queiroz Gisele Barbosa Victória Regina Thomaz de Oliveira Hélio de Mattos Alves Marina Amaral Alves Vanessa Carregaro João Santana da Silva Eliezer Jesus Barreiro Magna Suzana Alexandre-Moreira Lidia Moreira Lima Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity. PLoS ONE |
| title | Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity. |
| title_full | Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity. |
| title_fullStr | Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity. |
| title_full_unstemmed | Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity. |
| title_short | Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity. |
| title_sort | pre clinical evaluation of lassbio 1491 from in vitro pharmacokinetic study to in vivo leishmanicidal activity |
| url | https://doi.org/10.1371/journal.pone.0269447 |
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