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.
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UKCB2 1EW. richard.payne@sydney.edu.au
Richard J
RJ
Payne
Esther M M
EM
Bulloch
Olivier
O
Kerbarh
Chris
C
Abell
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