Phytoene Desaturase Inhibition by O-(2-Phenoxy)ethyl-N-aralkylcarbamates

Abstract

O-[1-Ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-benzylcarbamate exhibits a marked inhibition of carotenoid biosynthesis. Forty-one analogues were synthesized and assayed for plant-type phytoene desaturase (PDS) and zeta-carotene desaturase (ZDS) inhibition in a cell-free system using recombinant enzymes obtained from Escherichia coli transformants. The target enzyme of all carbamates synthesized in this study is PDS and not ZDS; no inhibition of ZDS was observed using a 10(-4) M inhibitor concentration. Four compounds, O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-phenylethyl)carbamate (23), O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-chlorobenzyl)carbamate (25), O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-chlorobenzyl)carbamate (26), and O-[1-methyl-2-(3-trifluoromethylphenoxy)]ethyl-N-benzylcarbamate (30), were the most potent PDS inhibitors. Their pI(50) values, the negative logarithms of the molar concentration that produces a 50% inhibition, were 7.5, representing the same inhibitory activity as norflurazon. With respect to a structure-activity relationship the oxygen atom of the phenoxy group and a carbamate structure in O-(1-ethyl-2-phenoxy)ethyl-N-aralkylcarbamates studied were found to be essential for strong PDS inhibitors. Also, introduction of an ethyl group at the alpha-position of the ethylene bridge between the phenoxy group and the carbamate was important for a strong PDS inhibitor. Substituents at the 2- and/or 3-position of the phenoxybenzene ring were found to be favorable to a strong PDS inhibition of the analogues.

The mechanism of diflufenican resistance and its inheritance in oriental mustard (Sisymbrium orientale L.) from Australia

“…Carotenoids are essential pigments which play important roles in plants, especially in photosynthesis . The desaturation sequence starting from phytoene in carotenoid biosynthesis has become the target of many bleaching herbicides . In previous studies on hydrilla, the presence of a mutation at Arg304 in the PDS gene resulted in the expression of a low level of resistance to fluridone (4‐ to 6‐fold) .…”

“…27,28 The desaturation sequence starting from phytoene in carotenoid biosynthesis has become the target of many bleaching herbicides. 29,30 In previous studies on hydrilla, the presence of a mutation at Arg304 in the PDS gene resulted in the expression of a low level of resistance to fluridone (4-to 6-fold). 17,18 No mutation, however, was present at this position in oriental mustard in this study.…”

Cross‐resistance to diflufenican and picolinafen and its inheritance in oriental mustard (Sisymbrium orientale L.)

“…15 The enzyme PDS, which initiates the desaturation sequence starting from phytoene in carotenoid biosynthesis, has been the target of many bleaching herbicides such as diflufenican and picolinafen. 16,17 These herbicides inhibit the formation of carotenoids 13,18,19 to cause a lack of carotenoids, destruction of chloroplast membranes and degradation of chlorophyll. This results in pronounced bleaching symptoms and necrosis of the tissues of susceptible plants, leading to plant death.…”

In silico target prediction for elucidating the mode of action of herbicides including prospective validation

“…31 In this work, taking into consideration this previous experience, we now attempted to extend the work of in silico target prediction to the area of agrochemicals, namely to herbicide target prediction and elucidation of modes of action (visualized in Figure 1). Figure 1 This herbicide dataset consisted of compounds tested on some of the well-explored herbicide targets that were organism specific (plant species), namely ACC (Acetyl-CoA carboxylase, Uniprot-Q94FR5) 6,33,34,35,36,37 , ALS (acetolactate synthase, Uniprot-Q94FR5) 6,33,7,38,39 , HPPD (4-hydroxyphenylpyruvate dioxygenase, Uniprot-P93836) 20,7,28,41,42,1 , PROTOX (protoporphyrinogen IX oxidase, Uniprot-Q9FYV8) 33,7,1,43,44 , and PDS (phytoene desaturase, Uniprot-P26294) 33,7,42,45,46 as well as a number of proprietary targets which cannot be mentioned in this study. The targets are from here on referred to as H01-H16.…”