Inhibition of chorismate-utilising enzymes by 2-amino-4-carboxypyridine and 4-carboxypyridone and 5-carboxypyridone analogues.
Several 2-amino-4-carboxypyridine, 4- and 5-carboxypyridone-based compounds were prepared and tested against three members of the chorismate-utilising enzyme family, anthranilate synthase, isochorismate synthase and salicylate synthase. Most compounds exhibited low micromolar inhibition of these three enzymes. The most potent inhibitor was a 4-carboxypyridone analogue bearing a lactate side chain on the pyridyl nitrogen which exhibited inhibition constants of 5, 91 and 54 muM against anthranilate synthase, isochorismate synthase and salicylate synthase respectively.
Payne
Richard J
RJ
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UKCB2 1EW. richard.payne@sydney.edu.au
Bulloch
Esther M M
EM
Kerbarh
Olivier
O
Abell
Chris
C
D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000878:Anthranilate Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D001419:Bacteria / Q000201:enzymology; D020134:Catalytic Domain; D002827:Chorismic Acid / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007539:Isonicotinic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008190:Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D000631:Aminopyridines; D004791:Enzyme Inhibitors; D007539:Isonicotinic Acids; D011725:Pyridines; D011728:Pyridones; D008190:Lyases; C022620:salicylate synthetase; D000878:Anthranilate Synthase; D019751:Intramolecular Transferases; C058486:isochorismate synthase; D002827:Chorismic Acid