BENZOYLPYRAZOLE

Toxicology

Pyrazolinate, Pyrazoxifen, Benzofenap, Topramezone and Pyrasulfotole are so far the benzoylpyrazole introduced into the herbicide market.

These compounds inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) n plants and animals. HPPD is an iron-dependent non-heme oxygenase involved in the metabolic pathway of tyrosine  with very different roles in prokaryote organisms, plants, and animal (Santucci  et al,2017).

Inhibition of HPPD leads to accumulation of tyrosine and and reduction in tyrosine toxic metabolites (assocciated with Type I Tyrosinemia disease-caused by inactivity of the fumaryl acetoacetate hydrolase (an enzyme downstream of HPPD itself (Santucci  et al,2017).

HPPD inhibitors have recently been shown to be effective in alkaptonuria, a disease due to dysfunction of homogentisate dioxygenase, another enzyme within the tyrosine metabolic pathway (Santucci  et al,2017).

Reference

Santucci A,  Bernardini G, Braconi D, Petricci E, and Manetti F (2017). 4‑Hydroxyphenylpyruvate Dioxygenase and Its Inhibition in Plantsand Animals: Small Molecules as Herbicides and Agents for theTreatment of Human Inherited Diseases. J. Med. Chem. 60,10, pg4101-4125. https://doi.org/10.1021/acs.jmedchem.6b01395

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