AI Article Synopsis
- A series of new N-benzylated phosphoramidate esters were created as analogues to fosmidomycin, which targets a specific enzyme in the malaria-causing Plasmodium falciparum parasite.
- These new compounds incorporate a 3,4-dihydroxyphenyl Mg-chelating group, replacing the original hydroxamic acid group in fosmidomycin, enhancing their effectiveness.
- The compounds demonstrated promising anti-parasitic activity, showing IC values between 5.6-16.4 µM against Plasmodium falciparum and 5.2-10.2 µM against Trypanosoma brucei brucei, with supportive data from computer models
Article Abstract
A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg-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-chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC values of 5.6-16.4 µM against Plasmodium falciparum parasites and IC 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) support their potential as PfDXR inhibitors.
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| http://dx.doi.org/10.1016/j.bioorg.2020.104280 | DOI Listing |
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