Synthesis and Biological Evaluation of Cyclopropyl Analogues of Fosmidomycin as Potent Plasmodium falciparum Growth Inhibitors

Journal of Medicinal Chemistry
2006.0

Abstract

A series of fosmidomycin analogues featuring restricted conformational mobility has been synthesized and evaluated as inhibitors of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase and as growth inhibitors of P. falciparum. The enantiomerically pure trans-cyclopropyl N-acetyl analogue 3b showed comparable inhibitory activity as fosmidomycin toward E. coli DOXP reductoisomerase and proved equally active when tested in vitro for P. falciparum growth inhibition. Conversely, the alpha-phenyl cis-cyclopropyl analogue 4 showed virtually no inhibition of the enzyme.

Knowledge Graph

Similar Paper

Synthesis and Biological Evaluation of Cyclopropyl Analogues of Fosmidomycin as Potent Plasmodium falciparum Growth Inhibitors
Journal of Medicinal Chemistry 2006.0
Synthesis of α-substituted fosmidomycin analogues as highly potent Plasmodium falciparum growth inhibitors
Bioorganic & Medicinal Chemistry Letters 2006.0
Synthesis and antimalarial evaluation of prodrugs of novel fosmidomycin analogues
Bioorganic & Medicinal Chemistry Letters 2015.0
Novel reverse thia-analogs of fosmidomycin: Synthesis and antiplasmodial activity
European Journal of Medicinal Chemistry 2019.0
Synthesis and Bioactivity of β-Substituted Fosmidomycin Analogues Targeting 1-Deoxy-<scp>d</scp>-xylulose-5-phosphate Reductoisomerase
Journal of Medicinal Chemistry 2015.0
Prodrugs of Reverse Fosmidomycin Analogues
Journal of Medicinal Chemistry 2015.0
Antimalarial and Structural Studies of Pyridine-Containing Inhibitors of 1-Deoxyxylulose-5-phosphate Reductoisomerase
ACS Medicinal Chemistry Letters 2013.0
Synthesis and evaluation of α,β-unsaturated α-aryl-substituted fosmidomycin analogues as DXR inhibitors
Bioorganic &amp; Medicinal Chemistry Letters 2007.0
Design, Synthesis, and X-ray Crystallographic Studies of α-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-<scp>d</scp>-xylulose 5-Phosphate Reductoisomerase
Journal of Medicinal Chemistry 2011.0
Alpha-Heteroatom Derivatized Analogues of 3-(Acetylhydroxyamino)propyl Phosphonic Acid (FR900098) as Antimalarials
Journal of Medicinal Chemistry 2013.0