Design, synthesis and structure-activity relationships of new phosphinate inhibitors of MurD.
A series of new phosphinate compounds were designed and synthesized as inhibitors of the d-glutamic acid-adding enzyme (MurD) involved in peptidoglycan biosynthesis. They were tested against the MurD enzyme from Escherichia coli, allowing initial structure-activity relationships to be deduced. Two compounds had IC(50) values near 100 microM and constitute a promising starting point for further development.
Strancar
Katja
K
University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
Blanot
Didier
D
Gobec
Stanislav
S
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D015394:Molecular Structure; D010453:Peptide Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis / Q000187:drug effects; D010721:Phosphinic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010457:Peptidoglycan; D010721:Phosphinic Acids; D010453:Peptide Synthases; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase