Novel Herbicidal Pyridazinone Cyclic Keto–Enol Compounds Inhibit Acetyl-CoA Carboxylase and Homogentisate Solanesyltransferase

Novel aryl cyclic keto-enol (aryl-CKE) derivatives containing a pyridazinone moiety (5-hydroxy-4-phenyl-3(2<i>H</i>)-pyridazinone) exhibit distinct herbicidal symptoms on grass and broadleaf weeds. Herbicide efficacy tests on target-site resistant blackgrass and enzyme inhibition assays revealed that the herbicidal activity in grassy weeds was primarily attributed to ACCase inhibition. The bleaching effect of the representative compounds on broadleaf plants was initially hypothesized to result from 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibition, based on physiological experiments. However, enzyme assays disproved HPPD inhibition. Sensitivity shift assays using overexpression lines of homogentisate solanesyl transferase (HST) in <i>Arabidopsis</i> and enzyme inhibition tests with <i>Chlamydomonas</i> HST enzyme heterologously expressed in <i>Escherichia coli</i> indicated that the compounds act as HST inhibitors. These findings demonstrate that the novel aryl-CKE derivatives containing a pyridazinone moiety possess dual modes of action, namely ACCase inhibition and HST inhibition, and are anticipated to be developed as a new tool for managing resistant weeds.