keyword
MENU ▼
Read by QxMD icon Read
search

microsome

keyword
https://www.readbyqxmd.com/read/28350454/structural-optimizations-of-thieno-3-2-b-pyrrole-derivatives-for-the-development-of-metabolically-stable-inhibitors-of-chikungunya-virus
#1
Kuan Chieh Ching, Thi Ngoc Quy Tran, Siti Naqiah Amrun, Yiu Wing Kam, Lisa F P Ng, Christina Li Lin Chai
Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus and there is no approved effective antiviral treatment currently available for CHIKV. We previously reported the discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activity against CHIKV infection in vitro. However, it has a short half-life in the presence of human liver microsomes (HLMs) (T1/2 = 2.91 min). Herein, we report further optimization studies in which potential metabolically labile sites on compound 1b were removed or modified, resulting in the identification of thieno[3,2-b]pyrrole 20 and pyrrolo[2,3-d]thiazole 23c possessing up to 17-fold increase in metabolic half-lives in HLMs and good in vivo pharmacokinetic properties...
March 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28345745/in-vitro-and-in-vivo-assessment-of-the-abuse-potential-of-pf614-a-novel-bio-md%C3%A2-prodrug-of-oxycodone
#2
D Lynn Kirkpatrick, William K Schmidt, Ricardo Morales, John Cremin, Julie Seroogy, Craig Husfeld, Thomas Jenkins
OBJECTIVE: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28342193/metabolism-of-the-tryptamine-derived-new-psychoactive-substances-5-meo-2-me-dalt-5-meo-2-me-alcht-and-5-meo-2-me-dipt-and-their-detectability-in-urine-studied-by-gc-ms-lc-ms-n-and-lc-hr-ms-ms
#3
Achim T Caspar, Jonas B Gaab, Julian A Michely, Simon D Brandt, Markus R Meyer, Hans H Maurer
Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using GC-MS, LC-MS(n) , and LC-HR-MS/MS. For metabolism studies, urine was collected over a 24-h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW)...
March 24, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28341741/endogenous-prostaglandin-e2-amplifies-il-33-production-by-macrophages-through-an-e-prostanoid-ep-2-ep4-cyclic-camp-epac-dependent-pathway
#4
Sachin K Samuchiwal, Barbara Balestrieri, Hannah Raff, Joshua A Boyce
When activated through toll-like receptors (TLRs), macrophages generate interleukin-33 (IL-33), an IL-1 family member that induces innate immune responses through ST2 signaling. Lipopolysaccharide (LPS), a TLR4 ligand, induces macrophages to generate prostaglandin E2 (PGE2) through inducible cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1) (1). We demonstrate that IL-33 production by bone marrow derived murine macrophages (bmMFs) requires the generation of endogenous PGE2 and the intrinsic expression of EP2 receptors to amplify NF-κB-dependent LPS-induced IL-33 expression via Exchange Protein Activated by cAMP (EPAC)...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28339283/development-optimization-and-implementation-of-a-centralized-metabolic-soft-spot-assay
#5
Anthony A Paiva, Cheryl Klakouski, Shu Li, Benjamin M Johnson, Yue-Zhong Shu, Jonathan Josephs, Tatyana Zvyaga, Ismael Zamora, Wilson Z Shou
AIM: High clearance is a commonly encountered issue in drug discovery. Here we present a centralized metabolic soft spot identification assay with adequate capacity and turnaround time to support the metabolic optimization needs of an entire discovery organization. METHODOLOGY: An integrated quan/qual approach utilizing both an orthogonal sample-pooling methodology and software-assisted structure elucidation was developed to enable the assay. Major metabolic soft spots in liver microsomes (rodent and human) were generated in a batch mode, along with kinetics of parent disappearance and metabolite formation, typically within 1 week of incubation...
March 24, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28338801/evolutionary-origin-of-mitochondrial-cytochrome-p450
#6
Tsuneo Omura, Osamu Gotoh
Different molecular species of cytochrome P450 (P450) are distributed between endoplasmic reticulum (microsomes) and mitochondria in animal cells. Plants and fungi have many microsomal P450s, but no mitochondrial P450 has so far been reported. To elucidate the evolutionary origin of mitochondrial P450s in animal cells, available evidence is examined, and the virtual absence of mitochondrial P450 in plants and fungi is confirmed. It is also suggested that a microsomal P450 is the ancestor of animal mitochondrial P450s...
March 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28338792/a-polygalacturonase-localized-in-the-golgi-apparatus-in-pisum-sativum
#7
Takao Ohashi, Jun Jinno, Yoshiyuki Inoue, Shoko Ito, Kazuhito Fujiyama, Takeshi Ishimizu
Pectin is a plant cell wall constituent that is mainly composed of polygalacturonic acid (PGA), a linear α1,4-D-galacturonic acid (GalUA) backbone. Polygalacturonase (PG) hydrolyzes the α1,4-linkages in PGA. Nearly all plant PGs identified thus far are secreted as soluble proteins. Here we describe the microsomal PG activity in pea (Pisum sativum) epicotyls and present biochemical evidence that it was localized to the Golgi apparatus, where pectins are biosynthesized. The microsomal PG was purified, and it was enzymatically characterized...
February 23, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28338641/nerolidol-and-farnesol-inhibit-some-cytochrome-p450-activities-but-did-not-affect-other-xenobiotic-metabolizing-enzymes-in-rat-and-human-hepatic-subcellular-fractions
#8
Alena Špičáková, Barbora Szotáková, Diana Dimunová, Zuzana Myslivečková, Vladimír Kubíček, Martin Ambrož, Kateřina Lněničková, Kristýna Krasulová, Pavel Anzenbacher, Lenka Skálová
Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they are principally taken as components of many folk medicines and dietary supplements. The aim of our study was to test and compare the potential inhibitory effect of acyclic sesquiterpenes, trans-nerolidol, cis-nerolidol and farnesol, on the activities of the main xenobiotic-metabolizing enzymes in rat and human liver in vitro. Rat and human subcellular fractions, relatively specific substrates, corresponding coenzymes and HPLC, spectrophotometric or spectrofluorometric analysis of product formation were used...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28337330/antimalarial-properties-of-simplified-kalihinol-analogues
#9
Mary Elisabeth Daub, Jacques Prudhomme, Choukri Ben Mamoun, Karine G Le Roch, Christopher D Vanderwal
Several kalihinol natural products, members of the broader isocyanoterpene family of antimalarial agents, are potent inhibitors of Plasmodium falciparum, the agent of the most severe form of human malaria. Our previous total synthesis of kalihinol B provided a blueprint to generate many analogues within this family, some as complex as the natural product and some much simplified and easier to access. Each analogue was tested for blood-stage antimalarial activity using both drug-sensitive and -resistant P. falciparum strains...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28335386/revisiting-the-metabolism-and-bioactivation-of-ketoconazole-in-human-and-mouse-using-liquid-chromatography-mass-spectrometry-based-metabolomics
#10
Ju-Hyun Kim, Won-Gu Choi, Sangkyu Lee, Hye Suk Lee
Although ketoconazole (KCZ) has been used worldwide for 30 years, its metabolic characteristics are poorly described. Moreover, the hepatotoxicity of KCZ limits its therapeutic use. In this study, we used liquid chromatography-mass spectrometry-based metabolomics to evaluate the metabolic profile of KCZ in mouse and human and identify the mechanisms underlying its hepatotoxicity. A total of 28 metabolites of KCZ, 11 of which were novel, were identified in this study. Newly identified metabolites were classified into three categories according to the metabolic positions of a piperazine ring, imidazole ring, and N-acetyl moiety...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332824/indole-substituted-benzothiazoles-and-benzoxazoles-as-selective-and-reversible-mao-b-inhibitors-for-treatment-of-parkinson-s-disease
#11
Min-Ho Nam, Moosung Park, Hyeri Park, Youngjae Kim, Seulki Yoon, Vikram Shahaji Sawant, Ji Won Choi, Jong-Hyun Park, Ki Duk Park, Sun-Joon Min, Changjoon Justin Lee, Hyunah Choo
To develop a novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was Compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 29 nM with no apparent effect on MAO-A activity at 10 M. Based on the reversibility assay, Compound 5b turned out to be a fully reversible with over 95% of recovery of enzyme activity after washout of the compound...
March 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28328618/clinical-implications-of-antimitochondrial-antibody-seropositivity-in-autoimmune-hepatitis-a-multicentre-study
#12
Paolo Muratori, Cumali Efe, Luigi Muratori, Ersan Ozaslan, Thomas Schiano, Eric M Yoshida, Alexandra Heurgué-Berlot, Claudine Lalanne, Marco Lenzi, Staffan Wahlin
BACKGROUND/AIM: Antimitochondrial antibody (AMA) positivity is the serological marker of primary biliary cholangitis (PBC), but can also be sporadically detected in autoimmune hepatitis (AIH). Little is known about the clinical significance of AMA in AIH. PATIENTS AND METHODS: We recruited 47 AMA-positive AIH cases from several centres and compared them with 264 well-characterized Italian AIH patients. Cases with any features of PBC were excluded. RESULTS: In univariate analysis, AMA-positive AIH patients were older (46 vs...
March 21, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28328322/novel-lc-ms-ms-and-high-throughput-mass-spectrometric-assays-for-monoacylglycerol-acyltransferase-inhibitors
#13
Jenson Qi, John A Masucci, Wensheng Lang, Margery A Connelly, Gary W Caldwell, Ioanna Petrounia, Jennifer Kirkpatrick, Alexander N Barnakov, Geoffrey Struble, Robyn Miller, Keli Dzordzorine, Gee-Hong Kuo, Michael Gaul, Alessandro Pocai, Seunghun Lee
Monoacylglycerol acyltransferase enzymes (MGAT1, MGAT2, and MGAT3) convert monoacylglycerol to diacylglycerol (DAG). MGAT1 and MGAT2 are both implicated in obesity-related metabolic diseases. Conventional MGAT enzyme assays use radioactive substrates, wherein the product of the MGAT-catalyzed reaction is usually resolved by time-consuming thin layer chromatography (TLC) analysis. Furthermore, microsomal membrane preparations typically contain endogenous diacylglycerol acyltransferase (DGAT) from the host cells, and these DGAT activities can further acylate DAG to form triglyceride (TG)...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28328319/discovery-of-human-intestinal-mgat-inhibitors-using-high-throughput-mass-spectrometry
#14
Ryutaro Adachi, Tsuyoshi Ishii, Shinichi Matsumoto, Takuya Satou, Junichi Sakamoto, Tomohiro Kawamoto
Monoacylglycerol acyltransferase (MGAT) activity catalyzes the synthesis of diacylglycerol (DAG) from fatty acyl-CoA and monoacylglycerol as substrates. It is important for the resynthesis of triacylglycerol (TAG) in the intestine. In the present study, we developed a MGAT enzymatic assay of human intestinal microsomes using a high-throughput mass spectrometry (MS)-based detection system. After screening with small-molecular-weight libraries for compounds exhibiting inhibitions against DAG and the consequent TAG syntheses, we identified multiple compounds that specifically inhibit intestinal MGAT activity...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28326038/ganoderic-acid-a-metabolites-and-their-metabolic-kinetics
#15
Fang-Rui Cao, Li Feng, Lin-Hu Ye, Li-Sha Wang, Bing-Xin Xiao, Xue Tao, Qi Chang
Ganoderic acid A (GAA), a representative active triterpenoid from Ganoderma lucidum, has been reported to exhibit antinociceptive, antioxidative, cytotoxic, hepatoprotective and anticancer activities. The present study aims (1) to identify GAA metabolites, in vivo by analyzing the bile, plasma and urine after intravenous administration to rats (20 mg/kg), and in vitro by incubating with rat liver microsomes (RLMs) and human liver microsomes (HLMs); (2) to investigate the metabolic kinetics of main GAA metabolites...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28325847/specialized-diacylglycerol-acyltransferase-contributes-to-extreme-fatty-acid-content-of-cuphea-seed-oil
#16
Umidjon Iskandarov, Jillian E Silva, Hae Jin Kim, Mariette Andersson, Rebecca E Cahoon, Keithanne Mockaitis, Edgar B Cahoon
Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn-2 and sn-3 positions of seed triacylglycerols (TAGs)...
March 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28325086/application-of-bacterial-reverse-mutation-assay-for-detection-of-non-genotoxic-carcinogens
#17
Rewan Kanode, Saurabh Chandra, Sharad Sharma
Non-genotoxic carcinogens may play a significant role in development of cancer. Currently short-term assays for mutagenicity classify genotoxic carcinogens and lack the abilities to detect epigenetic carcinogens. The need to develop an endpoint always remains to recognize potentially carcinogenic agents employing rapid and practical bioassays. For this, the present study utilized TA98 and TA1537 tester strains of Salmonella typhimurium to evaluate four non-genotoxic carcinogenic agents (Coumarin, β-Myrcene, Bis(2-ethylhexyl) phthalate and trans-anethole)...
March 22, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28322780/reductive-metabolism-of-tiaprofenic-acid-by-the-human-liver-and-recombinant-carbonyl-reducing-enzymes
#18
Petra Malátková, Adam Skarka, Kateřina Musilová, Vladimír Wsól
Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower Km value toward tiaprofenic acid than the cytosol (Km = 164 ± 18 μM vs. 569 ± 74 μM, respectively), whereas the cytosol showed higher specific activity during reduction than the microsomes (Vmax = 728 ± 52 pmol mg of protein(-1)·min(-1) vs...
March 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28322013/evidence-of-boldenone-nandrolone-5-10-estrene-3%C3%AE-17%C3%AE-diol-and-4-estrene-3-17-dione-as-minor-metabolites-of-testosterone-in-equine
#19
Jenny K Y Wong, David K K Leung, Peter Curl, Peter J Schiff, Kenneth K H Lam, Terence S M Wan
The detection of boldenone, nandrolone, 5(10)-estrene-3β,17α-diol and 4-estrene-3,17-dione in a urine sample collected from a gelding having been treated with testosterone (500 mg "Testosterone Suspension 100", single dose, injected intramuscularly) in 2009 led the authors' laboratory to suspect that these 'testicular' steroids could be minor metabolites of testosterone in geldings. Administration trials on six castrated horses with "Testosterone Suspension 100" confirmed that low levels of boldenone, nandrolone, 5(10)-estrene-3β,17α-diol and 4-estrene-3,17-dione could indeed be detected and confirmed in the early post-administration urine samples from all six geldings...
March 20, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28320984/investigation-of-antiaromatase-activity-using-hepatic-microsomes-of-nile-tilapia-oreochromis-niloticus
#20
Tanongsak Sassa-Deepaeng, Wasana Chaisri, Surachai Pikulkaew, Siriporn Okonogi
Microsomal aromatase enzymes of humans and rats have been used in antiaromatase assays, but enzyme activity is species-specific. The current study extracted hepatic microsomes of Nile tilapia (Oreochromis niloticus) to investigate and compare the antiaromatase activity of chrysin, quercetin, and quercitrin. This activity was evaluated using a dibenzylfluorescein (DBF) assay. Results revealed that the age and body weight of Nile tilapia affected the yield of extracted microsomes. Extraction of hepatic microsomes of Nile tilapia was most effective when using a reaction medium with a pH of 8...
March 19, 2017: Drug Discoveries & Therapeutics
keyword
keyword
116965
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"