Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg2+-chelating ligands.
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Fosfóricos
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Plasmodium falciparum
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Complexos de Coordenação
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Amidas
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Magnésio
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Antimaláricos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article