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Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg 2+ -chelating ligands.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2020 Dec; Vol. 105, pp. 104280. Date of Electronic Publication: 2020 Sep 17. - Publication Year :
- 2020
-
Abstract
- A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg <superscript>2+</superscript> -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 Mg <superscript>2+</superscript> -chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC <subscript>50</subscript> values of 5.6-16.4 µM against Plasmodium falciparum parasites and IC <subscript>50</subscript> 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) <superscript>5</superscript> support their potential as PfDXR inhibitors.<br /> (Copyright © 2020. Published by Elsevier Inc.)
- Subjects :
- Antimalarials pharmacology
Coordination Complexes pharmacology
Dose-Response Relationship, Drug
Drug Design
Fosfomycin analogs & derivatives
Fosfomycin pharmacology
HeLa Cells
Humans
Ligands
Molecular Docking Simulation
Trypanosoma brucei brucei drug effects
Amides chemical synthesis
Antimalarials chemical synthesis
Coordination Complexes chemical synthesis
Magnesium chemistry
Phosphoric Acids chemical synthesis
Plasmodium falciparum drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 105
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33152647
- Full Text :
- https://doi.org/10.1016/j.bioorg.2020.104280