Survey on the Recent Advances in 4-Hydroxyphenylpyruvate Dioxygenase (HPPD) Inhibition by Diketone and Triketone Derivatives and Congeneric Compounds: Structural Analysis of HPPD/Inhibitor Complexes and Structure-Activity Relationship Considerations

The serendipitous discovery of the HPPD inhibitors from allelopathic plants opened the way for searching new and effective herbicidal agents by application of classical hit-to-lead optimization approaches. A plethora of active and selective compounds were discovered that belong to three major classes of cyclohexane-based triketones, pyrazole-based diketones, and diketonitriles. In addition, to enhance inhibitory constant and herbicidal activity, many efforts were also made to gain broader weed control, crop safety, and eventual agricultural applicability. Moreover, HPPD inhibitors emerged as therapeutic agents for inherited and metabolic human diseases as well as vector-selective insecticides in the control of hematophagous arthropods. Given the large set of experimental data available, structure-activity relationship analysis could be used to derive suggestions for next generation optimized compounds.

Automated summary

The serendipitous discovery of HPPD inhibitors from allelopathic plants has paved the way for the search of new and effective herbicidal agents. Various active and selective compounds have been found, including cyclohexane-based triketones, pyrazole-based diketones, and diketonitriles. Efforts have also been made to enhance inhibitory constant and herbicidal activity, as well as to broaden weed control and ensure crop safety. HPPD inhibitors have also shown potential as therapeutic agents and insecticides. Structure-activity relationship analysis can provide suggestions for the development of next generation optimized compounds.