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Xiaoze Bao, Shiqiang Wei, Xingkai Qian, Jingping Qu, Baomin Wang, Liwei Zou, Guangbo Ge
A catalytic asymmetric [3 + 2] cyclization of novel 4-isothiocyanato pyrazolones and isatin-derived ketimines was developed, delivering a wide range of intriguing dispirotriheterocyclic products in high yield with excellent diastereoselectivity and enantioselectivity. A chiral sulfoxide derivative of this dispirocyclic product was identified to be a promising hit of the human carboxylesterase 1 inhibitor, and the significant difference of the activity between two enantiomers emphasized the importance of this asymmetric process...
May 22, 2018: Organic Letters
Ahmed Samir, Ayano Kage, Ohura Kayoko, Teruko Imai
1. Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ1 -cortienic acid (Δ1 -CA). 2. The simple high performance liquid chromatography method using acetic acid gradient was developed for the simultaneous determination of LE and its acidic metabolites. 3. LE was hydrolyzed in rat plasma with a half-life of 9 minutes...
May 21, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Jan M Falcke, Neelanjan Bose, Alexander B Artyukhin, Christian Rödelsperger, Gabriel V Markov, Joshua J Yim, Dominik Grimm, Marc H Claassen, Oishika Panda, Joshua A Baccile, Ying K Zhang, Henry H Le, Dino Jolic, Frank C Schroeder, Ralf J Sommer
In the nematodes Caenorhabditis elegans and Pristionchus pacificus, a modular library of small molecules control behavior, lifespan, and development. However, little is known about the final steps of their biosynthesis, in which diverse building blocks from primary metabolism are attached to glycosides of the dideoxysugar ascarylose, the ascarosides. We combine metabolomic analysis of natural isolates of P. pacificus with genome-wide association mapping to identify a putative carboxylesterase, Ppa-uar-1, that is required for attachment of a pyrimidine-derived moiety in the biosynthesis of ubas#1, a major dauer pheromone component...
May 14, 2018: Cell Chemical Biology
Laura Hedges, Susan Brown, A Kenneth MacLeod, Audrey Vardy, Edward Doyle, Gina Song, Marjory Moreau, Miyoung Yoon, Thomas G Osimitz, Brian G Lake
1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. 2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint ) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5...
May 21, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Emily N Dunn, Teresa M Ferrara-Bowens, Mark E Chachich, Cary L Honnold, Cristin C Rothwell, Heidi M Hoard-Fruchey, Catherine A Lesyna, Erik A Johnson, Douglas M Cerasoli, John H McDonough, C Linn Cadieux
Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase non-specifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure...
May 16, 2018: Toxicology Mechanisms and Methods
Xiaoxin Chen, Sheng He, Zhibin Liang, Qing X Li, Hai Yan, Jiye Hu, Xiaolu Liu
Pyraclostrobin has been widely and long-termly applicated to agricultural fields. The removal of pyraclostrobin from ecological environment has received wide attention. In this study, using sequential enrichments with pyraclostrobin as a sole carbon source, two microbial communities (HI2 and HI6) capable of catabolizing pyraclostrobin were obtained from Hawaiian soils. The microfloras analysis indicated that only Proteobacteria and Bacteroides could survive in HI2-soil after acclimatization, whereas the number of Proteobacteria in HI6-soil accounted for more than 99%...
April 27, 2018: Journal of Hazardous Materials
M Benjamin Barth, Katja Buchwalder, Akito Y Kawahara, Xin Zhou, Shanlin Liu, Nicolas Krezdorn, Björn Rotter, Ralf Horres, Anna K Hundsdoerfer
Background: The European spurge hawkmoth, Hyles euphorbiae (Lepidoptera, Sphingidae), has been intensively studied as a model organism for insect chemical ecology, cold hardiness and evolution of species delineation. To understand species isolation mechanisms at a molecular level, this study aims at determining genetic factors underlying two adaptive ecological trait candidates, phorbol ester (TPA) detoxification and seasonal cold acclimation. Method: A draft transcriptome of H...
2018: Frontiers in Zoology
Yuma Ishizaki, Tomomi Furihata, Yusuke Oyama, Kayoko Ohura, Teruko Imai, Masakiyo Hosokawa, Hidetaka Akita, Kan Chiba
Carboxylesterase 2 (CES2), which is a member of the serine hydrolase superfamily, is primarily expressed in the human small intestine, where it plays an important role in the metabolism of ester-containing drugs. Therefore, to facilitate continued progress in ester-containing drug development, it is crucial to evaluate how CES2-mediated hydrolysis influences its intestinal permeability characteristics. Human colon carcinoma Caco-2 cells have long been widely used in drug permeability studies as an enterocyte model...
2018: Biological & Pharmaceutical Bulletin
Hiroyoshi Koide, Masayuki Tsujimoto, Yurie Katsube, Megumi Ochiai, Ayako Hojo, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Daisuke Shima, Tetsuya Minegaki, Kohshi Nishiguchi
PURPOSE: Pharmacokinetics and pharmacodynamics of irinotecan have been reported to be altered in cancer patients with end-stage kidney disease (ESKD). Carboxylesterase (CES) has an important role in metabolism of irinotecan to its active metabolite, SN-38, in human liver. The purpose of the present study was to investigate whether CES activity was altered in ESKD patients. METHODS: The present study investigated the effects of uremic serum, uremic toxins, and fatty acids on the hydrolysis of irinotecan and a typical CES substrate, p-nitrophenyl acetate (PNPA), in human liver microsomes...
April 24, 2018: Cancer Chemotherapy and Pharmacology
Luis Claudio Cacciatore, Noemí Rosario Verrengia Guerrero, Adriana Cristina Cochón
Carbamate insecticides such as carbaryl and organophosphates such as azinphos-methyl share the ability to inhibit the activity of B-esterases. This study aimed to (1) assess the inhibitory effects of carbaryl on B-esterase activity in soft tissues and hemolymph of Planorbarius corneus; (2) establish whether binary mixtures of carbaryl and azinphos-methyl depart or not from a model of concentration addition on the inhibition of cholinesterase activity; (3) determine the bioconcentration and elimination of the pesticides...
April 14, 2018: Aquatic Toxicology
Mina Suh, Deborah Proctor, Grace Chappell, Julia Rager, Chad Thompson, Susan Borghoff, Lavorgie Finch, Robert Ellis-Hutchings, Karin Wiench
Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and copolymers for plastics, food packaging, adhesives, and cosmetic formulations. Although there is limited potential for human environmental exposure, occupational exposure can occur via inhalation and dermal contact. Recently, new genotoxicity data have been generated, along with in silico and in vitro read-cross analyses, for these acrylates. The availability of high-throughput screening (HTS) data through the ToxCast™/Tox21 databases allows for consideration of computational toxicology and organization of these data according to the ten key characteristics of carcinogens...
April 21, 2018: Toxicology
Mengjing Zhao, Tianpeng Zhang, Fangjun Yu, Lianxia Guo, Baojian Wu
Carboxylesterases (CES) are a family of phase I enzymes that play an important role in xenobiotic clearance and lipid metabolism. Here, we investigate a potential role of E4 promoter-binding protein 4 (E4bp4) in regulation of Ces and CPT-11 (irinotecan, a first-line drug for treating colorectal cancer) pharmacokinetics in mice. Mouse hepatoma Hepa-1c1c7 cells were transfected with Rev-erbα expression plasmid or siRNA targeting E4bp4. The relative mRNA and protein levels of Ces enzymes in the cells or the livers of wild-type and E4bp4-deficient (E4bp4-/- ) mice were determined by qPCR and Western blotting, respectively...
June 2018: Biochemical Pharmacology
Momoko Ishimine, Hyeon-Cheol Lee, Hirofumi Nakaoka, Hajime Orita, Toshiyuki Kobayashi, Konomi Mizuguchi, Mikumi Endo, Ituro Inoue, Koichi Sato, Takehiko Yokomizo
Irinotecan (CPT-11) is an anticancer prodrug that is activated by the carboxylesterase CES2 and has been approved for the treatment of many types of solid tumors, including colorectal cancer. Recent studies with cell lines show that CES2 expression is regulated by the tumor suppressor protein p53. However, clinical evidence for this regulatory mechanism in cancer is lacking. In this study, we examined the relationship between TP53 gene status and CES2 expression in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37) showed lower CES2 mRNA levels (≥1...
2018: Disease Markers
Xuegui Wang, Xing Xiang, Huiling Yu, Shuhua Liu, Yong Yin, Peng Cui, Yaqiong Wu, Jing Yang, Chunxian Jiang, Qunfang Yang
The beet armyworm Spodoptera exigua, a major pest affecting numerous cultivated crops in China, has developed a serious resistance to many traditional chemical insecticides. The resistance levels of the field-collected populations from different districts in Sichuan Province, China, to nine insecticides were detected with a diet-incorporation bioassay. Compared to the Lab-ZN strain, five (in 2014) and three (in 2016) field populations displayed either high or extremely high levels of resistance to beta-cypermethrin...
April 2018: Pesticide Biochemistry and Physiology
Kimberly Baumgardner, Connie Lin, Richard A Firtel, Jesus Lacal
The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mold Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as cAMP, secreted during starvation to move toward the sources of the signal. Previous work demonstrated that the gskA gene encodes the Dictyostelium homologue of glycogen synthase kinase 3 (GSK3), a highly conserved serine/threonine kinase, which plays a major role in the regulation of Dictyostelium chemotaxis...
April 6, 2018: Environmental Microbiology
Bradley J Main, Amanda Everitt, Anthony J Cornel, Fereydoun Hormozdiari, Gregory C Lanzaro
BACKGROUND: Malaria mortality rates in sub-Saharan Africa have declined significantly in recent years as a result of increased insecticide-treated bed net (ITN) usage. A major challenge to further progress is the emergence and spread of insecticide resistance alleles in the Anopheles mosquito vectors, like An. coluzzii. A non-synonymous mutation in the para voltage-gated sodium channel gene reduces pyrethroid-binding affinity, resulting in knockdown resistance (kdr). Metabolic mechanisms of insecticide resistance involving detoxification genes like cytochrome P450 genes, carboxylesterases, and glutathione S-transferases are also important...
April 4, 2018: Parasites & Vectors
Yi Cheng, Hailian Zang, Hailan Wang, Dapeng Li, Chunyan Li
Chlorimuron-ethyl is a typical long-term residual sulfonylurea herbicide whose long period of residence poses a serious hazard to rotational crops. Microbial degradation is considered to be the most acceptable method for its removal, but the degradation mechanism is not clear. In this work, we investigated gene expression changes during the degradation of chlorimuron-ethyl by an effective chlorimuron-ethyl-degrading bacterium, Rhodococcus erythropolis D310-1. The genes that correspond to this degradation and their mode of action were identified using RNA-Seq and qRT-PCR...
March 31, 2018: Ecotoxicology and Environmental Safety
Xiao Yang, Juan Dai, Sujuan Zhao, Rong Li, Tim Goulette, Xianggui Chen, Hang Xiao
BACKGROUND: Organophosphate and carbamate pesticide residues in food and the environment pose a great threat to human health, and have made the easy and rapid detection of these pesticide residues an important task. Discovering new enzyme sources from plants can help reduce the cost of large-scale applications of rapid pesticide detection via enzyme inhibition. RESULTS: Plant esterase from kidney bean was purified. Kidney bean esterase is identified as a carboxylesterase by substrate and inhibitor specificity tests and mass spectrometry identification...
March 31, 2018: Journal of the Science of Food and Agriculture
Jing Xu, Jin-Chun Qiu, Xing Ji, Hong-Li Guo, Xuan Wang, Bo Zhang, Tengfei Wang, Feng Chen
Herbal products have grown steadily across the globe over the past 10 years and have increasingly been incorporated into western medicine for healthcare aims, thereby causing potential pharmacokinetic herb-drug interactions (HDI) through the inhibition or induction of drug-metabolizing enzymes and transporters. Human carboxylesterases 1 (CES1) and 2 (CES2) are versatile enzymes involvement in the metabolism of endogenous and exogenous compounds including many important therapeutic medications. Moreover, the growing number of CES substrate drugs also underscores the importance of CES1 and CES2...
March 30, 2018: Current Drug Metabolism
Chi Zeng, Lingbing Wu, Yao Zhao, Yueli Yun, Yu Peng
Background: Tea is one of the most economically important crops in China. However, the tea geometrid ( Ectropis obliqua ), a serious leaf-feeding pest, causes significant damage to tea crops and reduces tea yield and quality. Spiders are the most dominant predatory enemies in the tea plantation ecosystem, which makes them potentially useful biological control agents of E. obliqua . These highlight the need for alternative pest control measures. Our previous studies have shown that tea saponin (TS) exerts insecticidal activity against lepidopteran pests ...
2018: PeerJ
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