Abstract
Reverse hydroxamate-based inhibitors of IspC, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. The binding mode of one derivative in complex with EcIspC and a divalent metal ion was clarified by X-ray analysis. Pilot experiments have demonstrated in vivo potential.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aldose-Ketose Isomerases / antagonists & inhibitors*
-
Aldose-Ketose Isomerases / chemistry
-
Animals
-
Antimalarials / chemical synthesis*
-
Antimalarials / chemistry
-
Antimalarials / pharmacology
-
Crystallography, X-Ray
-
Erythrocytes / drug effects
-
Erythrocytes / parasitology
-
Fosfomycin / analogs & derivatives*
-
Fosfomycin / chemical synthesis
-
Fosfomycin / chemistry
-
Fosfomycin / pharmacology
-
Humans
-
Malaria / drug therapy
-
Mice
-
Models, Molecular
-
Molecular Structure
-
Multienzyme Complexes / antagonists & inhibitors*
-
Multienzyme Complexes / chemistry
-
Oxidoreductases / antagonists & inhibitors*
-
Oxidoreductases / chemistry
-
Parasitic Sensitivity Tests
-
Plasmodium berghei
-
Plasmodium falciparum / drug effects*
-
Plasmodium falciparum / enzymology
-
Structure-Activity Relationship
Substances
-
Antimalarials
-
Multienzyme Complexes
-
Fosfomycin
-
fosmidomycin
-
Oxidoreductases
-
1-deoxy-D-xylulose 5-phosphate reductoisomerase
-
Aldose-Ketose Isomerases