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Pyrazolidine‐3,5‐dione‐based inhibitors of phosphoenolpyruvate carboxylase as a new class of potential C 4 plant herbicides
Author(s) -
Dick Markus,
Erlenkamp German,
Nguyen Giang T.T.,
Förster Kerstin,
Groth Georg,
Gohlke Holger
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12842
Subject(s) - phosphoenolpyruvate carboxylase , pyruvate carboxylase , enzyme , chemistry , stereochemistry , biochemistry , in vitro , phosphoenolpyruvate carboxykinase
Phosphoenolpyruvate carboxylase ( PEPC ) is a key enzyme in the C 4 photosynthetic pathway of many of the world's worst weeds and a valuable target to develop C 4 plant‐selective herbicides. By virtual screening, analog synthesis, and in vitro validation, we identified pyrazolidine‐3,5‐diones as a new class of small molecules with inhibitory potential down to the submicromolar range against C 4 PEPC and a selectivity factor of up to 16 over C 3 PEPC . No other biological activity has yet been reported for the best compound, (3‐bromophenyl)‐4‐(3‐hydroxybenzylidene)‐pyrazolidine‐3,5‐dione. A systematic variation in the substituents allowed the derivation of a qualitative structure–activity relationship. These findings make this compound class highly interesting for further investigations toward generating potent, C 4 plant‐selective herbicides with a low potential for unwanted effects.