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Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg2+-chelating ligands.
Adeyemi, Christiana M; Hoppe, Heinrich C; Isaacs, Michelle; Mnkandhla, Dumisani; Lobb, Kevin A; Klein, Rosalyn; Kaye, Perry T.
Afiliação
  • Adeyemi CM; Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa.
  • Hoppe HC; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
  • Isaacs M; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
  • Mnkandhla D; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
  • Lobb KA; Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
  • Klein R; Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
  • Kaye PT; Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Department of Biochemistry and Microbiolgy, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa. Electronic address: P.Kaye@ru.a
Bioorg Chem ; 105: 104280, 2020 12.
Article em En | MEDLINE | ID: mdl-33152647
ABSTRACT
A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg2+-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-d-xylulose-5-phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg2+-chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC50 values of 5.6-16.4 µM against Plasmodium falciparum parasites and IC50 values of 5.2 - 10.2 µM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)5 support their potential as PfDXR inhibitors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Fosfóricos / Plasmodium falciparum / Complexos de Coordenação / Amidas / Magnésio / Antimaláricos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Fosfóricos / Plasmodium falciparum / Complexos de Coordenação / Amidas / Magnésio / Antimaláricos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article