• Korean Journal of Environmental Agriculture
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• v.42 no.2
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• pp.139-151
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• 2023

Sulfonylurea herbicides are widely used in agriculture because they have a long residual period and high selectivity. An analytical method was developed using QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) technique for simultaneous determination of sulfonylurea herbicide residues in agricultural products by liquid chromatography tandem mass spectrometry and for establishment MRL (Maximum Residue Limit) of those herbicides in Korea. Extraction was performed using acetonitrile containing 0.1% formic acid with MgSO₄ (anhydrous magnesium sulfate) and NaCl (sodium chloride) and the extract was cleaned up using MgSO₄ and C₁₈ (octadecyl). The matrix-matched calibration curves were composed of 7 concentration levels from 0.001 to 0.25 mg/kg and their coefficients of determination (R²) exceeded 0.99. The recoveries of three spiking levels (LOQ, 10LOQ, 50LOQ, n=5) were in the range of 71.7-114.9% with relative standard deviations of less than 20.0% for all the five agriculture products. All validation values met criteria of the European Union SANTE/11312/2021 guidelines and Food and Drug Safety Evaluation guidelines. Therefore, the proposed analytical method was accurate, effective, and sensitive for sulfonylurea herbicide residues determination in agricultural commodities.

• Korean Journal of Weed Science
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• v.15 no.1
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• pp.54-62
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• 1995

Acetolactate synthase activity inhibition and herbicidal activities were investigated with 2 sulfonylureas [chlorsulfuron{2-chloro-N-{{(4-methoxy-6-methyl-1,3,5-triazin-2-yl) amino} carboxyl} benzenesulfonamide}, metsulfuron-methyl{methyl-2{{{{(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino}carbonyl}amino}sulfonyl}benzoic acid}, and 2 imidazoli-nones [imazethapyr{2-{4,5-dihydro-4-methyl-4-(1-methyl)-5-oxo-1H-imidazol-2-yl}-5-ethyl-3-pyridinecarboxylicacid}, imazaquin{2-{4,5-dihydro-4-methyl-4-(1-methyl)-5-oxo-1H-imidazol-2-yl}-3-quinoline carboxylic acid} herbicides. A broad weeding spectrum was observed with the treated herbicides at low application rates. Both corn(Zea mays L.) and sorghum(Sorghum bicolor Moench) were very sensitive to the two herbicide groups. Although legumes, such as soybean(Glycine max Merr.), clover(Trifolium repense L.), and indian jointvetch(Aeschnomene indica L.) were sensitive to the sulfonylureas, they were tolerant to the imidazolinones. On the contrary, wheat(Triticum aestivum L.) and barley(Hoderum sativum Jess.) showed the reverse responses of the legumes to the two herbicide groups. Quackgrass(Agropyron repens(L.) P. Beauv.). however, was commonly tolerant to the two herbicide groups. Degrees of crop injury and acetolactate synthase inhibition also varied with the crops examined. The 50% inhibition concentrations of sulfonylureas on acetolactate synthase in vitro activity($IC_{50}$) from corn, wheat, and soybean did not relate to the greenhouse herbicidal activities ($GI_{50}$). With chlorsulfuron, for example, wheat had more than 100 times higher $GI_{50}$ than corn and soybean, but the $IC_{50}$ was 4 to 10 times lower. Similar observation was made with metsulfuron-methyl. However, closer relationships between $IC_{50}$ and $GI_{50}$ were found with the imidazolinones. When imazethapyr was applied, the order of $GI_{50}$ values against com, wheat, and soybean was the same as that of $IC_{50}$.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.329-336
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• 1995

Conformational free energy calculations using an empirical potential function and a hydration shell model(program CONBIO) were carried out on hypoglycemic agent acetohexamide and tolazamide in the unhydrated and hydrated states. The initial geometry of sulfonylureas was obtained from X-ray crystallographieal data and homologous molecular fragments. In both states, the feasible conformations were obtained from the calculations of conformational energy, conformational entropy, and hydration free energy by varying all the torsion angles of the molecules. From the calculation results, it is known that the conformations] entropy is the major contribution to stabflize the low-free-energy conformations of two sulfonylureas in both states. But, in hydrated state, the hydration does not directly affect each conformations. The intramolecular hydrogen bonding of sulfonylurea hydrogen and 7-membered nitrogen appeared to the conformations of tolazamide in both states. It is thought that the hydrogen bonding decrease steric hindrance on the receptor binding direction. The substitution of alicyclic or N-heterocyclic ring than that of carbons chain of urea moiety may be properly interaction between sulfonylureas and the putative pancreatic receptor.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.570-580
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• 1996

Design and synthesis of novel 4-phenyl-1-arylsulfonylimidazolones 3 and 4-phenyl-3-arylsulfonylimidazolones 4 and evaluation of their cytotoxic activity against eleven human cancer cell lines and two murine leukemia cell lines in vitro were performed. As a result, a series of 4-phenyl-1(N)-arylsulfonylimidazolones (3) has been found to be the potential anticancer agent. Compounds 3b, 3c, and 3d exhibit strong activity as indicated by their $IC_{50}$ values 0.39, 3.19, $0.31{\mu}g/mL$ against A549 and 0.80, 0.48, $0.0007{\mu}g/mL$against SK-Mel-2, respectively. These compounds also possess much more potent activity (10-1000 times) than LY186641 against eleven other cell lines.

• Bulletin of the Korean Chemical Society
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• v.11 no.2
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• pp.144-149
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• 1990

Conformational free energy calculations using an empirical potential function (ECEPP/2) and the hydration shell model were carried out on the sulfonylurea herbicides of bensulfuron methyl (Londax) and metsulfuron methyl (Ally). The conformational energy was minimized from starting conformations which included possible combinations of torsion angles in the molecule. The conformational entropy of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecule in aqueous solution, the hydration free energy of each group was calculated and compared each other. It was found that the low-free-energy conformations of two molecules in aqueous solution prefer the overall folded structure, in which an interaction between the carbonyl group of ester in aryl ring and the first amido group of urea bridge plays an important role. From the analysis of total free energy, the hydration and conformational entropy are known to be essential in stabilizing low-free-energy conformations of Londax, whereas the conformational energy is proved to be a major contribution to the total free energy of low-free-energy conformations of Ally.

• 대한임상약리학회:학술대회논문집
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• 2002.12a
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• pp.5-5
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• 2002

• KOREAN JOURNAL OF CROP SCIENCE
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• v.48 no.4
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• pp.286-291
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• 2003

Monochoria vaginalis is one of the most troublesome resistant weeds in Korean rice culture. Thus, the objectives of this study were to evaluate the response of M. vaginalis resistant to sulfonylurea(SU) herbicides and to determine alternative herbicides for the control of resistant M. vaginalis in direct seeded and transplanted rice culture in Korea. In greenhouse studies, the resistant biotype was 31-, 38-, 3172-, and 7-fold more resistant to ben-sulfuron-methyl, cyclosulfamuron, imazosulfuron, and pyrazosulfuron-ethyl, respectively, than the susceptible biotype, indicating cross-resistance to the SU herbicides used in this study. Non-SU herbicides, butachlor, carfentrazone-ethyl, mefenacet, pretilachlor, pyrazolate, and thiobencarb, several SU herbicide-based mixtures, ethoxysulfuron plus fentrazamide, pyrazosulfuron-ethyl plus pyrazolate plus simetryn, and non-SU herbicide-based mixtures, pyrazolate plus butachlor, pyrazolate plus pretilachlor, simetryn plus molinate, carfentrazone-ethyl plus butachlor, and carfentrazone-ethyl plus thiobencarb can be used to control both the resistant and susceptible biotypes of M. vaginalis when applied before the second leaf stage. In the field experiment, the resistant biotype of M. vaginalis that survived from the paddy fields treated with a SU herbicide-based mixture could effectively be controlled by using mixtures of bentazone plus MCPA, bentazone plus mecoprop-P, and bentazone plus 2,4-D when applied at 2 or 4 main leaves. Our results suggest that the SU-resistant M. vaginalis had not developed multiple resistances to herbicides with different modes of action. In particular, bentazone plus MCPA and bentazone plus mecoprop-P were effective control measures after failure to control resistant M. vaginalis in Korean rice culture.

• Journal of the Korean Chemical Society
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• v.41 no.6
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• pp.304-312
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• 1997

Acetolactate synthase(ALS) is the common enzyme in the biosynthetic of valine, leucine, and isoleucine, and is the target of several classes of structually unrelated herbicides, including sulfonylureas, imidazolinones, and triazolopyrimidines. In an effort to develop new and desirable herbicides, we have synthesized 4,6-dimethoxypyrimidine derivatives, and examined their inhibitory activities on pea ALS. The most active compound was found to be K11570 and $IC_{50}$ value for K11570 was 0.2 ${\mu}M.$ The inhibition of pea ALS by K11570 was biphasic, showing increased inhibition with incubation time. The K11570 showed mixed-type inhibition with respect to substrate pyruvate. Dual inhibition analysis of K11570 versus sufonylurea herbicide Ally and feedback inhibitor leucine revealed that three inhibitors were competitive for binding to ALS. The arginine modified enzyme showed decreased inhibition by K11570, sufonylurea Ally, and leucine, in constrast to, tryptophan modification did not affect on the sensitivity of ALS to the inhibitors.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.433-441
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• 2001

The ATP-sensitive potassium $(K_{ATP})$) channel is a member of inward rectifier potassium channel (Kir) that is inhibited by intracellular ATP and functions in close relation to sulfonylurea receptors (SUR). Although the molecular mechanism and physiological function of $K_{ATP}$ channels are well understood, the expression pattern during development or treatment with the channel modulators such as glybenclamide is little known. In this work, we determined mRNA levels of a $K_{ATP}$ channel (Kir6.2) and a sulfonylurea receptor (SUR2) in rat tissues by RNase protection assay. Levels of Kir6.2 and SUR2 mRNA in the rat brain and skeletal muscle were higher in adult $(90{\sim}120\;days)$ than in neonate $(2{\sim}8\;days),$ whereas those in the heart were not much different between neonate $(2{\sim}8\;days)$ and adult $(90{\sim}120\;days).$ In addition, none of $K_{ATP}$ channel modulators (opener, pinacidil and nicorandil; blocker, glybenclamide) affected the Kir6.2 mRNA levels in the heart, brain and skeletal muscle. The results indicate that the expression of Kir and SUR genes can vary age-dependently, but the expression of Kir is not dependent on the long-term treatment of channel modulators. The effect of the channel modulators on mRNA level of SUR is remained to be studied further.

• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.947-952
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• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.