Protoporphyrinogen-IX-oxidase Inhibitors

Pyraflufen-ethyl is also used as the defoliant for cotton and as a desiccant for potatoes. Pyraflufen-ethyl is a novel inhibitor of protoporphyrinogen IX oxidase. Inhibition of this enzyme in chloroplasts causes accumulation of protoporphyrinogen IX, which results in peroxidation of foliar cell membrane lipids under the light and finally death of cells. 

Uracil derivatives can also function as herbicides by inhibition of the enzyme protoporphyrinogen-IX-oxidase (PRO), which is involved in the biosynthesis of chlorophyll <2006H(68)561>. Commercial examples of such PPO inhibitors include isocil 1104, bromacil 1105, terbacil 1106, flupropacil 1107, lenacil 1108, butafenacil 1109, and benzfendizone 1110 (Figure 9). 

Figure 6. Binding site region of Protoporphyrinogen IX Oxidase 2 [Protox, pdb code ISEZ) with the co-crystallized inhibitor /NH (ball and sticks representation), the critical amino acid residue arginine (Arg) and the co-factor FAD. Re-docked solutions are indicated inside (int) and outside (ext) of the detected binding pocket.

Fig. 3.20. Protox inhibitor 4-bromo-3-(5-carboxy-4-chloro-2-fluorophenyl)-l-methyl-5-trifluoromethylpyrazole (79) used in protoporphyrinogen IX oxidase binding studies.

Compounds 292-295 act as inhibitors of protoporphyrinogen oxidase (Protox) - an enzyme in the chloroplasts of the plant cells that oxidizes protoporphyrinogen IX (303) to produce protoporphyrin IX (304) (Scheme 66) [261], In turn, 304 is a precursor molecule for both chlorophyll and heme. When protoporphyrinogen oxidase is inhibited, protoporphyrinogen IX is accumulated and transferred from chloroplasts into the cytoplasm, where non-enzymatic conversion of 303 to 304 occurs. When present in cytoplasm, 304 is cytotoxic due to interaction with oxygen upon action of light, which results in formation of singlet O2 molecules. O2 causes lipid peroxidation, membrane disruption and plant cell death. 

Analysis of the pigment profiles in extracts of developing chloroplasts treated with the aryltriazinediones, indicated a build-up of protoporphyrin IX, a recognized potent photosensitizer capable of initiating free radical reactions f21.22L The aryltriazinediones did not have an effect on the ability of the chloroplasts to convert protoporphyrin IX into Mg protoporphyrin IX, but were found to be sensitive inhibitors of protoporphyrinogen oxidase (a PI5Q... 

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