Design, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds.
Arch Pharm (Weinheim)
; 353(8): e1900325, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-32484266
ABSTRACT
A series of thiazolopyrimidine derivatives was designed and synthesized as a Leishmania major pteridine reductase 1 (LmPTR1) enzyme inhibitor. Their LmPTR1 inhibitor activities were evaluated using the enzyme produced by Escherichia coli in a recombinant way. The antileishmanial activity of the selected compounds was tested in vitro against Leishmania sp. Additionally, the compounds were evaluated for cytotoxic activity against the murine macrophage cell line RAW 264.7. According to the results, four compounds displayed not only a potent in vitro antileishmanial activity against promastigote forms but also low cytotoxicity. Among them, compound L16 exhibited an antileishmanial activity for both the promastigote and amastigote forms of L. tropica, with IC50 values of 7.5 and 2.69 µM, respectively. In addition, molecular docking studies and molecular dynamics simulations were also carried out in this study. In light of these findings, the compounds provide a new potential scaffold for antileishmanial drug discovery.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases
/
Pirimidinas
/
Tiazóis
/
Desenho de Fármacos
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Leishmania major
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Inibidores Enzimáticos
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Antiprotozoários
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Ano de publicação:
2020
Tipo de documento:
Article