N-acylated sulfonamide congeners of fosmidomycin lack any inhibitory activity against DXR.
The antibiotic fosmidomycin (3a) is an inhibitor of the non-mevalonate pathway for isoprenoid biosynthesis. Four analogues in which an acylated sulfonamide group is substituting for its phosphonate moiety have been synthesized in a fruitless effort to preserve one negative charge in order to increase the accompanying affinity for 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the fosmidomycin target enzyme.
Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Bharat
B
Gadakh
Department of Chemistry, University of Namur, Rue de Bruxelles 61, Namur B-5000, Belgium.
Jenny
J
Pouyez
Department of Chemistry, University of Namur, Rue de Bruxelles 61, Namur B-5000, Belgium.
Johan
J
Wouters
Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Akkaladevi
A
Venkatesham
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Paul
P
Cos
Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Arthur
A
Van Aerschot
D000215:Acylation; D019747:Aldose-Ketose Isomerases / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D004926:Escherichia coli / Q000201:enzymology; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D013449:Sulfonamides; D005578:Fosfomycin; C024640:fosmidomycin; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases
Antimalarial; DXR inhibitors; Fosmidomycin; N-Acyl sulfonamides