Design and synthesis of novel N-benzylidenesulfonohydrazide inhibitors of MurC and MurD as potential antibacterial agents.
A series of novel N-benzylidenesulfonohydrazide compounds were designed and synthesized as inhibitors of UDP-N-acetylmuramic acid: L-alanine ligase (MurC) and UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase (MurD) from E. coli, involved in the biosynthesis of bacterial cell-walls. Some compounds possessed inhibitory activity against both enzymes with IC(50) values as low as 30 microM. In addition, a new, one-pot synthesis of amidobenzaldehydes is reported.
Frlan
Rok
R
University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
Kovac
Andreja
A
Blanot
Didier
D
Gobec
Stanislav
S
Pecar
Slavko
S
Obreza
Ales
A
D002384:Catalysis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction / Q000187:drug effects; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D011108:Polymers; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012236:Rhodanine / Q000737:chemistry
D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D011108:Polymers; D011724:Pyridazines; D012236:Rhodanine; D010453:Peptide Synthases; C023229:UDP-N-acetylmuramoyl-alanine synthetase; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase