Kim TH

References (17)

Title : Enzymatic transformation products of phloretin as potent anti-adipogenic compounds - Jeong_2021_Biosci.Biotechnol.Biochem__
Author(s) : Jeong GH , Cho JH , Park EK , Kim TH
Ref : Biosci Biotechnol Biochem , : , 2021
Abstract : Enzymatic structure modification of the representative chalcone phloretin (1) with polyphenol oxidase from Agaricus bisporus origin produced two new biphenyl-type phloreoxin (2) and phloreoxinone (3), and a previously undescribed (2R)-5,7,3",5"-tetrahydroxyflavanone (4). The structure of these new oxidized products 2-4 elucidated by interpreting the spectroscopic data (NMR and FABMS) containing the absolute stereochemistry established by analysis of the circular dichroism (CD) spectrum. Compared to the original phloretin, the new products (2) and (3) showed highly improved anti-adipogenic potencies both toward pancreatic lipase and accumulation of 3T3-L1 cells. Aslo, phloreoxin (2) effectively inhibited the expression of C/EBPbeta, PPARgamma, and aP2 at the mRNA level in the 3T3 adipocytes. Thus, phloreoxin (2), containing a biphenyl moiety catalyzed by A. bisporus polyphenol oxidase, have the potential to influence the anti-adipogenic capacity.
ESTHER : Jeong_2021_Biosci.Biotechnol.Biochem__
PubMedSearch : Jeong_2021_Biosci.Biotechnol.Biochem__
PubMedID: 34610084

Title : Structures and Biosynthetic Pathway of Coprisamides C and D, 2-Alkenylcinnamic Acid-Containing Peptides from the Gut Bacterium of the Carrion Beetle Silpha perforata - Shin_2021_J.Nat.Prod_84_239
Author(s) : Shin YH , Ban YH , Kim TH , Bae ES , Shin J , Lee SK , Jang J , Yoon YJ , Oh DC
Ref : Journal of Natural Products , 84 :239 , 2021
Abstract : Coprisamides C and D (1 and 2) were isolated from a gut bacterium, Micromonospora sp. UTJ3, of the carrion beetle Silpha perforata. Based on the combined analysis of UV, MS, and NMR spectral data, the planar structures of 1 and 2 were elucidated to be unreported derivatives of coprisamides A and B, cyclic depsipeptides bearing a 2-alkenylcinnamic acid unit and the unusual amino acids beta-methylaspartic acid and 2,3-diaminopropanoic acid. The absolute configuration of 1 was determined using the advanced Marfey's method, phenylglycine methyl ester derivatization, and J-based configuration analysis. The biosynthetic gene clusters for the coprisamides were investigated based on genomic data from coprisamide-producing strains Micromonospora sp. UTJ3 and Streptomyces sp. SNU533. Coprisamide C (1) was active against the Mycobacterium tuberculosis mc(2) 6230 strain.
ESTHER : Shin_2021_J.Nat.Prod_84_239
PubMedSearch : Shin_2021_J.Nat.Prod_84_239
PubMedID: 33497210
Gene_locus related to this paper: strsq-a0a890ctl7

Title : Novel Hybrid Molecules Based on (-)-Epigallocatechin Gallate as Potent Anti-adipogenic Agents - Jeong_2020_Chem.Pharm.Bull.(Tokyo)_68_1155
Author(s) : Jeong GH , Cho JH , Jo C , Park S , Kim SB , Kim TH
Ref : Chem Pharm Bull (Tokyo) , 68 :1155 , 2020
Abstract : A series of novel (-)-epigallocatechin gallate (EGCG)-phloroglucinol hybrid compounds 1-4 has been successfully synthesized by employing a simple and efficient methodology using a dielectric barrier discharge (DBD) plasma irradiation. The new hybrid structures were determined by interpretation of spectroscopic data, with the absolute configurations being established by analysis of the circular dichroism (CD) spectra. The novel hybrids 1 and 2 showed highly improved anti-adipogenic potencies toward both pancreatic lipase and preadipocytes differentiation in 3T3-L1 compared to the original EGCG and phloroglucinol. A novel hybrid 1 represent an interesting subclass of anti-adipogenic candidates that need further research.
ESTHER : Jeong_2020_Chem.Pharm.Bull.(Tokyo)_68_1155
PubMedSearch : Jeong_2020_Chem.Pharm.Bull.(Tokyo)_68_1155
PubMedID: 33268647

Title : ARS2\/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages - Yin_2020_Nat.Commun_11_2978
Author(s) : Yin J , Kim SS , Choi E , Oh YT , Lin W , Kim TH , Sa JK , Hong JH , Park SH , Kwon HJ , Jin X , You Y , Kim JH , Kim H , Son J , Lee J , Nam DH , Choi KS , Shi B , Gwak HS , Yoo H , Iavarone A , Park JB
Ref : Nat Commun , 11 :2978 , 2020
Abstract : The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates beta-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.
ESTHER : Yin_2020_Nat.Commun_11_2978
PubMedSearch : Yin_2020_Nat.Commun_11_2978
PubMedID: 32532977

Title : Multilayer Engineering of Enzyme Cascade Catalysis for One-Pot Preparation of Nylon Monomers from Renewable Fatty Acids - Kim_2020_ACS.Catal_10_4871
Author(s) : Kim TH , Kang SH , Han JE , Seo EJ , Jeon EY , Choi GE , Park JB , Oh DK
Ref : ACS Catal , 10 :4871 , 2020
Abstract : Enzyme cascade catalysis has critical problems in obtaining the high concentrations of products, such as the low stabilities and activities of biocatalysts and the inhibition by hydrophobic reactants at high concentrations to biocatalysts. Here, we performed multilayer engineering of enzyme cascade catalysis to produce C11 nylon monomers at commercially viable concentrations from ricinoleic acid. The catalysis was driven by engineered Escherichia coli-based whole-cell biocatalysts and cell-free enzymes (i.e., lipases). Stabilities and activities of the biocatalysts were improved by engineering the bottleneck enzyme BaeyerVilliger monooxygenase and introducing a cofactor regeneration system. The inhibitory effects of the byproducts n-heptanoic acid and pyruvate on the cascade enzymes were overcome, and the products were simply recovered in situ by engineering of reactions with the addition of an adsorbent resin. We obtained 248 mM undecanedioic acid or 232 mM 11-aminoundecanoic acid as a nylon monomer from 300 mM ricinoleic acid by multilayer engineering. The concentration was 500- and 640-fold higher than those produced by nonengineering, respectively. We have also simply isolated the C11 nylon monomers via solvent extraction to a rather high purity. This study will contribute to the industrial enzyme cascade synthesis of nylon monomers in an environmentally-friendly route from renewable biomass.
ESTHER : Kim_2020_ACS.Catal_10_4871
PubMedSearch : Kim_2020_ACS.Catal_10_4871

Title : Substrate-Based Allosteric Regulation of a Homodimeric Enzyme - Mehrabi_2019_J.Am.Chem.Soc_141_11540
Author(s) : Mehrabi P , Di Pietrantonio C , Kim TH , Sljoka A , Taverner K , Ing C , Kruglyak N , Pomes R , Pai EF , Prosser RS
Ref : Journal of the American Chemical Society , 141 :11540 , 2019
Abstract : Many enzymes operate through half-of-the sites reactivity wherein a single protomer is catalytically engaged at one time. In the case of the homodimeric enzyme, fluoroacetate dehalogenase, substrate binding triggers closing of a regulatory cap domain in the empty protomer, preventing substrate access to the remaining active site. However, the empty protomer serves a critical role by acquiring more disorder upon substrate binding, thereby entropically favoring the forward reaction. Empty protomer dynamics are also allosterically coupled to the bound protomer, driving conformational exchange at the active site and progress along the reaction coordinate. Here, we show that at high concentrations, a second substrate binds along the substrate-access channel of the occupied protomer, thereby dampening interprotomer dynamics and inhibiting catalysis. While a mutation (K152I) abrogates second site binding and removes inhibitory effects, it also precipitously lowers the maximum catalytic rate, implying a role for the allosteric pocket at low substrate concentrations, where only a single substrate engages the enzyme at one time. We show that this outer pocket first desolvates the substrate, whereupon it is deposited in the active site. Substrate binding to the active site then triggers the empty outer pocket to serve as an interprotomer allosteric conduit, enabling enhanced dynamics and sampling of activation states needed for catalysis. These allosteric networks and the ensuing changes resulting from second substrate binding are delineated using rigidity-based allosteric transmission theory and validated by nuclear magnetic resonance and functional studies. The results illustrate the role of dynamics along allosteric networks in facilitating function.
ESTHER : Mehrabi_2019_J.Am.Chem.Soc_141_11540
PubMedSearch : Mehrabi_2019_J.Am.Chem.Soc_141_11540
PubMedID: 31188575
Gene_locus related to this paper: rhopa-q6nam1

Title : A new approach to procyanidins synthesis with potent anti-adipogenic effects - Jeong_2019_Bioorg.Med.Chem.Lett_29_2079
Author(s) : Jeong GH , Cho JH , Kim TH
Ref : Bioorganic & Medicinal Chemistry Lett , 29 :2079 , 2019
Abstract : Convenient structure modification of (+)-catechin (1) induced by nonthermal dielectric barrier discharge (DBD) plasma treatment afforded three novel methylene-linked flavan-3-ol oligomers, methylenetetracatechin (2), methylenetricatechin (3), and methylenedicatechin (4), together with two known catechin dimers, bis 8,8'-catechinylmethane (5) and bis 6,8'-catechinylmethane (6). The structures of the three new catechin oligomers 2-4 with methylene bridges were elucidated by detailed 1D- and 2D-NMR analysis, and the absolute configurations were established by the observation of circular dichroism (CD). The novel products 2 and 3 showed significantly enhanced anti-adipogenic capacities against both pancreatic lipase and differentiation of 3T3-L1 preadipocytes compared to the parent (+)-catechin.
ESTHER : Jeong_2019_Bioorg.Med.Chem.Lett_29_2079
PubMedSearch : Jeong_2019_Bioorg.Med.Chem.Lett_29_2079
PubMedID: 31300342

Title : The role of dimer asymmetry and protomer dynamics in enzyme catalysis - Kim_2017_Science_355_
Author(s) : Kim TH , Mehrabi P , Ren Z , Sljoka A , Ing C , Bezginov A , Ye L , Pomes R , Prosser RS , Pai EF
Ref : Science , 355 : , 2017
Abstract : Freeze-trapping x-ray crystallography, nuclear magnetic resonance, and computational techniques reveal the distribution of states and their interconversion rates along the reaction pathway of a bacterial homodimeric enzyme, fluoroacetate dehalogenase (FAcD). The crystal structure of apo-FAcD exhibits asymmetry around the dimer interface and cap domain, priming one protomer for substrate binding. This asymmetry is dynamically averaged through conformational exchange on a millisecond time scale. During catalysis, the protomer conformational exchange rate becomes enhanced, the empty protomer exhibits increased local disorder, and water egresses. Computational studies identify allosteric pathways between protomers. Water release and enhanced dynamics associated with catalysis compensate for entropic losses from substrate binding while facilitating sampling of the transition state. The studies provide insights into how substrate-coupled allosteric modulation of structure and dynamics facilitates catalysis in a homodimeric enzyme.
ESTHER : Kim_2017_Science_355_
PubMedSearch : Kim_2017_Science_355_
PubMedID: 28104837
Gene_locus related to this paper: rhopa-q6nam1

Title : Hepatic role in an early glucose-lowering effect by a novel dipeptidyl peptidase 4 inhibitor, evogliptin, in a rodent model of type 2 diabetes - Kim_2016_Eur.J.Pharmacol_771_65
Author(s) : Kim TH , Kim MK , Cheong YH , Chae YN , Lee Y , Ka SO , Jung IH , Shin CY , Bae EJ , Son MH
Ref : European Journal of Pharmacology , 771 :65 , 2016
Abstract : Although multiple dipeptidyl peptidase 4 (DPP4) inhibitors have shown glucose-lowering effects by preserving pancreatic cells in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice, the hepatic role in regulation of glucose homeostasis by DPP4 inhibitors in HFD/STZ mice remains elusive. In herein study, parallel comparison of effects on the liver (expression of gluconeogenic genes and the linked signaling molecules) and pancreas (islet morphology and relative area of alpha or beta cells) in combination with glucose-lowering effects were made at the end of 2- and 10-week of evogliptin treatment in HFD/STZ mice. Significant control of hyperglycemia was observed from the second week and persisted during 10-week treatment of 0.3% evogliptin in HFD/STZ mice. This effect was accompanied by increased level of plasma glucagon-like peptide-1 and preserved pancreas islet structure. Furthermore, the hepatic increases in gluconeogenic gene expression in HFD/STZ mice was significantly reduced by evogliptin treatment, which was accompanied by the suppression of cAMP response element-binding protein (CREB) phosphorylation and expression of transducer of regulated CREB protein 2. This hepatic effect of evogliptin treatment was reproduced in 2-week study, however, pancreatic beta-cell area was not altered yet although the expression of pancreatic and duodenal homeobox protein 1 was increased. We conclude that the suppression of hepatic gluconeogenesis by evogliptin is followed by preservation of pancreatic islet, leading to remarkable and persistent glucose-lowering effect in HFD/STZ mice. Our findings provide further insight for the hepatic role in DPP4 inhibitor-mediated glucose control in diabetes.
ESTHER : Kim_2016_Eur.J.Pharmacol_771_65
PubMedSearch : Kim_2016_Eur.J.Pharmacol_771_65
PubMedID: 26621343

Title : Rubus coreanus Miquel Ameliorates Scopolamine-Induced Memory Impairments in ICR Mice - Choi_2014_J.Med.Food_17_1049
Author(s) : Choi MR , Lee MY , Hong JE , Kim JE , Lee JY , Kim TH , Chun JW , Shin HK , Kim EJ
Ref : J Med Food , 17 :1049 , 2014
Abstract : ABSTRACT The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.
ESTHER : Choi_2014_J.Med.Food_17_1049
PubMedSearch : Choi_2014_J.Med.Food_17_1049
PubMedID: 25121635

Title : Pancreatic lipase inhibitory gallotannins from Galla Rhois with inhibitory effects on adipocyte differentiation in 3T3-L1 cells - Kwon_2013_Molecules_18_10629
Author(s) : Kwon OJ , Bae JS , Lee HY , Hwang JY , Lee EW , Ito H , Kim TH
Ref : Molecules , 18 :10629 , 2013
Abstract : Activity-guided isolation of a methanolic extract of Galla Rhois using pancreatic lipase and 3T3-L1 adipocytes led to the isolation of seven phenolic compounds: protoaphin-fb (1), 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-beta-D-glucose (2), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (3), 1,2,4,6-tetra-O-galloyl-beta-D-glucose (4), 3-hydroxy-5-methoxy-phenol 1-O-beta-D-glucoside (5), methylgallate (6), and gallic acid (7). Their structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and compounds 1-5 exhibited potent inhibitory effects on this enzyme, with IC50 values ranging from 30.6 +/- 2.4 to 3.5 +/- 0.5 mM. In addition, the highly galloylated compound 2 was also found to induce potent inhibition of adipocyte differentiation in 3T3-L1 cells.
ESTHER : Kwon_2013_Molecules_18_10629
PubMedSearch : Kwon_2013_Molecules_18_10629
PubMedID: 24002138

Title : Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis - Kim_2012_Plant.Cell_24_5177
Author(s) : Kim TH , Kunz HH , Bhattacharjee S , Hauser F , Park J , Engineer C , Liu A , Ha T , Parker JE , Gassmann W , Schroeder JI
Ref : Plant Cell , 24 :5177 , 2012
Abstract : In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor-nucleotide binding-Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid-induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest.
ESTHER : Kim_2012_Plant.Cell_24_5177
PubMedSearch : Kim_2012_Plant.Cell_24_5177
PubMedID: 23275581
Gene_locus related to this paper: arath-eds1 , arath-PAD4

Title : Pancreatic lipase inhibition by C-glycosidic flavones Isolated from Eremochloa ophiuroides - Lee_2010_Molecules_15_8251
Author(s) : Lee EM , Lee SS , Chung BY , Cho JY , Lee IC , Ahn SR , Jang SJ , Kim TH
Ref : Molecules , 15 :8251 , 2010
Abstract : Activity-guided fractionation of a methanolic extract of the leaves of Eremochloa ophiuroides (centipede grass) using a pancreatic lipase inhibitory assay led to the isolation and identification of a new C-glycosidic flavone, luteolin 6-C-ss-D-boivinopyranoside (1), as well as eight known compounds. The structures of these compounds were established on the basis of interpretation of their spectroscopic data. Among these isolates, the C-glycosidic flavones 1-5 showed potent inhibitory effects on pancreatic lipase, with IC(5)(0) values ranging from 18.5 +/- 2.6 to 50.5 +/- 3.9 muM.
ESTHER : Lee_2010_Molecules_15_8251
PubMedSearch : Lee_2010_Molecules_15_8251
PubMedID: 21081855

Title : Interactions of acetylcholinesterase with caveolin-1 and subsequently with cytochrome c are required for apoptosome formation - Park_2008_Carcinogenesis_29_729
Author(s) : Park SE , Jeong SH , Yee SB , Kim TH , Soung YH , Ha NC , Kim ND , Park JY , Bae HR , Park BS , Lee HJ , Yoo YH
Ref : Carcinogenesis , 29 :729 , 2008
Abstract : Acetylcholinesterase (AChE) is emerging as an important component in leading to apoptosis. Our previous study demonstrated that silencing of the AChE gene blocked the interaction between cytochrome c and apoptotic protease-activating factor-1 (Apaf-1) in etoposide-induced apoptosis of HT-29 cells. We undertook this study to further dissect the molecular role of AChE in apoptosome formation. The present study elicited that small interfering RNA (siRNA) to cytochrome c gene blocked the interaction of AChE with Apaf-1, whereas siRNA to Apaf-1 gene did not block the interaction of AChE with cytochrome c, indicating that the interaction of AChE with cytochrome c is required for the interaction between cytochrome c and protease-activating factor-1. We further observed that AChE is localized to caveolae via interacting with caveolin-1 during apoptosis and that the disruption of caveolae prevented apoptosome formation. These data indicate that the interactions of AChE with caveolin-1 and subsequently with cytochrome c appear to be indispensable for apoptosome formation.
ESTHER : Park_2008_Carcinogenesis_29_729
PubMedSearch : Park_2008_Carcinogenesis_29_729
PubMedID: 18258603

Title : Temporospatial localization of acetylcholinesterase activity in the dental epithelium during mouse tooth development - Ko_2007_Life.Sci_81_1235
Author(s) : Ko SO , Kim TH , Lee HK , Lee JC , Cho ES
Ref : Life Sciences , 81 :1235 , 2007
Abstract : Acetylcholinesterase (AChE), a principal modulator of cholinergic neurotransmission, also has been demonstrated to be involved in the morphogenetic processes of neuronal and non-neuronal tissues. This study shows that AChE exhibits temporospatial activity in the dental epithelium of the developing mouse tooth. To identify the AChE activity in the mouse tooth during development, we performed enzyme histochemistry on the mouse embryos from embryonic day 13 (E13) to E18 and on the incisors and molars of the neonatal mouse at 10 days after birth (P10). In the developing molars of mouse embryos, AChE activity was not found in the dental epithelium at E13 (bud stage). AChE activity first appeared in the developing cervical loops of the enamel organ at E14 (cap stage), but was not found in the enamel knot. At E18 (bell stage), AChE activity was localized in the inner enamel epithelium except the cervical-loop area. In the incisors and molars of neonatal mice (P10), AChE activity was localized in the inner enamel epithelium of the cervical-loop and enamel-free area. Overall, AChE activity was localized in the differentiating dental epithelium while the activity of butyrylcholinesterse, another cholinesterase, was located primarily in the cells of the dental follicle. The results suggest that AChE may play a role in the histo- and cytodifferentiation of dental epithelium during tooth development.
ESTHER : Ko_2007_Life.Sci_81_1235
PubMedSearch : Ko_2007_Life.Sci_81_1235
PubMedID: 17905311

Title : [Synthesis of reactivators of phosphorylated acetylcholinesterase of bis-pyridiniumdialdoxime type with a 3-oxapentane connecting chain and their testing in vitro on a model of the enzyme inhibited by chlorpyrifos and methylchlorpyrifos] - Musilek_2006_Ceska.Slov.Farm_55_115
Author(s) : Musilek K , Kuca K , Jun D , Dohnal V , Kim TH , Jung YS , Dolezal M
Ref : Ceska a Slovenska Farmacie , 55 :115 , 2006
Abstract : Insecticides (e.g., parathion, chlorpyrifos, methylchlorpyrifos) and nerve agents (e.g.. soman, sarin, tabun, VX) belong to the group of organophosphates. They are able to irreversibly inhibit the enzyme acetylcholinesterase (AChE). Three new reactivators with a 3-oxapentane connecting chain were prepared. The ability of the new compounds to reactivate AChE inhibited by pesticides was tested in vitro and compared to known oxime 10(-3) M which is unfortunately not applicable to in vivo experiments. All tested compounds are practically ineffective for methylchlorpyrifos-inhibited AChE at the physiological concentration (10(-5) M). On the other hand, the known reactivators surpass new substances in the case of chlorpyrifos-inhibited AChE at both concentrations.
ESTHER : Musilek_2006_Ceska.Slov.Farm_55_115
PubMedSearch : Musilek_2006_Ceska.Slov.Farm_55_115
PubMedID: 16838488

Title : Design and synthesis of new bis-pyridinium oxime reactivators for acetylcholinesterase inhibited by organophosphorous nerve agents - Kim_2005_Bioorg.Med.Chem.Lett_15_2914
Author(s) : Kim TH , Kuca K , Jun D , Jung YS
Ref : Bioorganic & Medicinal Chemistry Lett , 15 :2914 , 2005
Abstract : New bis-pyridinium oxime reactivators connected with a CH(2)CH(2)OCH(2)CH(2) linker between two pyridinium rings were designed and synthesized. In the test of their potency to reactivate AChE inhibited by cyclosarin, the bis-pyridinium oxime 6b achieved reactivation potency higher than 10% at the lower concentration 10(-4)M.
ESTHER : Kim_2005_Bioorg.Med.Chem.Lett_15_2914
PubMedSearch : Kim_2005_Bioorg.Med.Chem.Lett_15_2914
PubMedID: 15911280