Synthesis and evaluation of 2,5-dihydrochorismate analogues as inhibitors of the chorismate-utilising enzymes.
A library of 2,5-dihydrochorismate analogues were designed as inhibitors of the chorismate-utilising enzymes including anthranilate synthase, isochorismate synthase, salicylate synthase and 4-amino-4-deoxychorismate synthase. The inhibitors were synthesised in seven or eight steps from shikimic acid, sourced from star anise. The compounds exhibited moderate but differential inhibition against the four chorismate-utilising enzymes.
Payne
Richard J
RJ
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UKCB2 1EW. payne@chem.usyd.edu.au
Bulloch
Esther M M
EM
Toscano
Miguel M
MM
Jones
Michelle A
MA
Kerbarh
Olivier
O
Abell
Chris
C
D000878:Anthranilate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002827:Chorismic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008190:Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012706:Serratia marcescens / Q000201:enzymology; D000637:Transaminases
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D000637:Transaminases; C066599:aminodeoxychorismate synthase; D008190:Lyases; C022620:salicylate synthetase; D000878:Anthranilate Synthase; D019751:Intramolecular Transferases; C058486:isochorismate synthase; D019731:Carbon-Nitrogen Ligases; D002827:Chorismic Acid