Acetohydroxyacid Synthase Inhibitors Research Articles

Bis-pyrimidylpyrazolinones - a new class of acetohydroxy-acid synthase (AHAS) inhibitor

Hydroxypyrazolinones which bear two pyrimidine rings (on N-1 and C-4) were found to be potent inhibitors of acetohydroxy-acid synthase which displayed good herbicidal activity in vivo. Structure–activity relationship studies suggested the presence of a second binding niche on the enzyme for a 4,6-dimethoxypyrimidine ring.

Bis‐pyrimidylpyrazolinones – a new class of acetohydroxy‐acid synthase (AHAS) inhibitor

Hydroxypyrazolinones which bear two pyrimidine rings (on N-1 and C-4) were found to be potent inhibitors of acetohydroxy-acid synthase which displayed good herbicidal activity in vivo. Structure–activity relationship studies suggested the presence of a second binding niche on the enzyme for a 4,6-dimethoxypyrimidine ring.

5356789 Methods for detecting acetohydroxyacid synthase inhibitors : Shaner Dale L Lawrenceville, NJ, United States Assigned to American Cyanamid Company

5356789 Methods for detecting acetohydroxyacid synthase inhibitors : Shaner Dale L Lawrenceville, NJ, United States Assigned to American Cyanamid Company

5356789 Methods for detecting acetohydroxyacid synthase inhibitors : Dale L Shaner assigned to American Cyanamid Company

5356789 Methods for detecting acetohydroxyacid synthase inhibitors : Dale L Shaner assigned to American Cyanamid Company

Effect of Imazamethabenz on Histology and Histochemistry of Polysaccharides in the Main Shoot of Wild Oat (Avena fatua)

Imazamethabenz, an acetohydroxyacid synthase (AHAS)-inhibiting herbicide, was applied at a sublethal rate (200 g ai ha–1) to foliage of greenhouse-grown wild oat plants at the 2-leaf stage without tillers. Main shoot tissues were sampled 1 to 2 wk after imazamethabenz treatment and prepared for light microscopic examination. Histological observations showed that imazamethabenz treatment did not produce drastic changes on leaf structures but did affect chloroplast integrity of fully expanded 2nd leaf and inhibited differentiation of the young 3rd leaf 1 wk after application. The internode length and the number of cells in internodes of the herbicide-treated main stem were greatly reduced, presumably due to the inhibition by imazamethabenz of intercalary meristem cell division in early stages of internode elongation. One week after imazamethabenz application, histochemical studies revealed an increased accumulation of starch granules in chloroplasts of the 2nd leaf but reduced starch levels in the main stem. This confirmed the hypothesis that AHAS inhibitors affected phloem transport of photosynthates.

Modeling root absorption and translocation of 5‐substituted analogs of the imidazolinone herbicide, imazapyr

AbstractQuantitative structure‐activity relationships (QSAR) were developed between the physicochemical parameters of the 5‐substituent of a series of analogs of the imidazolinone herbicide, imazapyr, and root absorption, translocation, inhibition of acetohydroxyacid synthase (AHAS), and herbicidal activity of the analogs. An optimum substituent lipophilicity (π = 1.85–2–3) for root absorption was identified for corn (Zea mays L.) and sunflower (Helianthus annuus L.). Translocation from roots to shoots was greatest for those analogs having either highly nonpolar or highly polar 5‐substituents, indicating that both symplastic and apopiastic mechanisms may be functioning. In addition, translocation from roots was positively correlated with electron‐withdrawing parameters of the 5‐substituent, and a possible mechanism governing this relationship is discussed. Modeling in vitro AHAS inhibition was not successful, but models were developed for herbicidal activity as measured in an Arabidopsis thaliana (L.) Hevnh. bioassay. The whole‐plant models described an optimum substituent lipophilicity (π = 0 71) which probably reflected the influence of this parameter on the component processes of absorption and translocation. Whole‐plant activity was also greater for analogs having electron‐donating 5‐substituents; this result suggests that electron donation may be important for metabolism, or more likely, for AHAS inhibition.

Phytotoxicity of Acetohydroxyacid Synthase Inhibitors Is Not Due to Accumulation of 2-Ketobutyrate and/or 2-Aminobutyrate.

Acetohydroxyacid synthase (AHAS) is the site of action of herbicides of different chemical classes, such as imidazolinones, sulfonylureas, and triazolopyrimidines. Inhibition of AHAS causes the accumulation of 2-ketobutyrate (2-KB) and 2-aminobutyrate (2-AB) (the transamination product of 2-KB), and it has been proposed that the phytotoxicity of these inhibitors is due to this accumulation. Experiments were done to determine the relationship between accumulation of 2-KB and 2-AB and the phytotoxicity of imazaquin to maize (Zea mays). Imazaquin concentrations that inhibit growth of maize plants also cause the accumulation of 2-KB and 2-AB in the shoots. Supplementation of imazaquin-treated plants with isoleucine reduced the pools of 2-KB and 2-AB in the plant but did not protect plants from the growth inhibitory effects of imazaquin. Conversely, feeding 2-AB to maize plants increased 2-KB and 2-AB pools to much higher levels than those observed in imazaquin-treated plants, yet such high pools of 2-KB and 2-AB in the plant had no significant effect on growth. These results conclusively demonstrate that growth inhibition following imazaquin treatment is not due to accumulation of 2-KB and/or 2-AB in plants. Changes in the amino acid profiles after treatment with imazaquin suggest that starvation for the branched-chain amino acids may be the primary cause of growth retardation of maize.

Primisulfuron herbicide-resistant tobacco plants: mutant selection in vitro by adventitious shoot formation from culturéd leaf discs

A simple procedure has been developed for the rapid and direct selection of herbicide-resistant mutant plants. The procedure uses adventitious shoot formation from suitable explants, such as leaf discs, on a shoot-inducing culture medium containing a toxic herbicide concentration. Resistant green shoots were thus isolated from tobacco ( Nicotiana tabacum L.) leaf explants cultured on medium containing 100 μg 1 −1 primisulfuron, a new sulfonylurea herbicide. Resistant shoots were recovered from both haploid and diploid explants after UV mutagenesis, as well as without mutagenic treatment. Three mutant plants of separate origin were further analyzed biochemically and genetically. Their acetohydroxyacid synthase (AHAS) enzyme activity was less inhibited by sulfonylurea herbicides than that of unselected, sensitive wild type plants. The extent of inhibition of the AHAS enzyme among the three mutants was different for different sulfonylurea and imidazolinone herbicides suggesting different sites were affected by each mutation. Herbicide tolerance was scored for germinating seedling populations and was found to be inherited as a single dominant nuclear gene. Adventitious shoot formation from cultured leaf discs was used to determine the cross tolerance of mutant plants to various herbicidal AHAS inhibitors. The usefulness of this rapid and direct scheme for mutant selection based on adventitious shoot formation or embryogenesis is discussed.

Acetohydroxyacid Synthase Inhibitors: N-Phthalyl-ʟ-valine Anilide and Related Compounds

The potency of L-valine as an inhibitor of Zea mays acetohydroxyacid synthase (AHAS) is increased more than 8000-fold on conversion to its N-phthalyl anilide derivative which is active at 2 microM. The D-valine, alpha-aminobutyric acid, isoleucine and phenylalanine analogs are 11- to 43-fold less potent, and similar N-phthalyl anilide derivatives of other branched-chain amino acids are essentially inactive. Full potency is retained on replacing the phthalimide moiety of the valine anilide with cyclohexane-1,2-dicarboximide or 1-cyclohexene-1,2-dicarboximide groups and partial activity with 4-cyclohexene-1,2-dicarboximide and methyl- or dimethylmaleimide groups. Inhibition of the enzyme and of root growth by the valine derivatives may result from binding at or near the site involved in feedback control of AHAS by L-valine.

Imidazolinones

The imidazolinones, a new chemical class of herbicides, were shown to be uncompetitive inhibitors of acetohydroxyacid synthase from corn. This is the first common enzyme in the biosynthetic pathway for valine, leucine, and isoleucine. The K(i) for the imidazolinones tested ranged from 2 to 12 micromolar. These results may explain the mechanism of action of these new herbicides.

Inhibition of acetohydroxy acid synthase by leucine

The enzymatic reaction of acetohydroxy acid synthase in crude extracts of Escherichia coli K-12 is inhibited by leucine. Inhibition is most pronounced at low pH values and is low at pH values higher than 8.0. Both isoenzymes of acetohydroxy acid synthase present in E. coli K-12 (isoenzyme I and isoenzyme III) are inhibited by leucine. Isoenzyme I, which is responsible for the majority of acetohydroxy acid synthase activity in E. coli K-12 at physiological pH, is inhibited almost completely by 30 mM leucine at pH 6.25–7.0 and is not affected at all at pH values higher than 8.4. Inhibition of isoenzyme I by leucine is a mixed noncompetitive process. Leucine inhibition of isoenzyme III is pH-independent and reaches only 40% at 30 mM leucine. The inhibition of acetohydroxy acid synthase by leucine at physiological pH, observed in vitro in this study, correlates with the idea that acetohydroxy acid synthase is a target for the toxicity of the abnormally high concentrations of leucine in E. coli K-12.

Substrate channeling: alpha-ketobutyrate inhibition of acetohydroxy acid synthase in Salmonella typhimurium.

Excess alpha-ketobutyrate inhibited the growth of Salmonella typhimurium LT2 by inhibiting the acetohydroxy acid synthase-catalyzed synthesis of alpha-acetolactate (a valine precursor). As a result, cells were starved for valine, and both ilvB (encoding acetohydroxy acid synthase I) and ilvGEDA (ilvG encodes acetohydroxy acid synthase II) were derepressed. The addition of valine reversed the effects of alpha-ketobutyrate.