keyword
MENU ▼
Read by QxMD icon Read
search

Cytochrome P450

keyword
https://www.readbyqxmd.com/read/28535350/activation-of-phenyl-4-2-oxo-3-alkylimidazolidin-1-yl-benzenesulfonates-prodrugs-by-cyp1a1-as-new-antimitotics-targeting-breast-cancer-cells
#1
Sébastien Fortin, Xavier Charest-Morin, Vanessa Turcotte, Coraline Lauvaux, Jacques Lacroix, Marie-France Côté, Stéphane Gobeil, Rene C-Gaudreault
Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs), that are antimicrotubule prodrugs activated by CYP1A1. Although PAIB-SOs are inert in most cells tested, they are highly cytocidal towards several human breast cancer cells, including hormone-independent and chemoresistant types...
May 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28535034/p450-mediated-non-natural-cyclopropanation-of-dehydro-alanine-containing-thiopeptides
#2
Joshua G Gober, Swapnil V Ghodge, Jonathan W Bogart, Walter J Wever, Richard R Watkins, Eric M Brustad, Albert A Bowers
Thiopeptides are a growing class of ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. Many biosynthetic enzymes for RiPPs, especially thiopeptides, are promiscuous and can accept a wide range of peptide substrates with different amino acid sequence; thus, these enzymes have been used as tools to generate new natural product derivatives. Here, we explore an alternative route to molecular complexity by engineering thiopeptide tailoring enzymes to do new or non-native chemistry...
May 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28534261/the-role-of-drug-metabolites-in-the-inhibition-of-cytochrome-p450-enzymes
#3
Momir Mikov, Maja Đanić, Nebojša Pavlović, Bojan Stanimirov, Svetlana Goločorbin-Kon, Karmen Stankov, Hani Al-Salami
Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28533430/heme-thiolate-sulfenylation-of-human-cytochrome-p450-4a11-functions-as-a-redox-switch-for-catalytic-inhibition
#4
Matthew E Albertolle, Donghak Kim, Leslie D Nagy, Chul-Ho Yun, Ambra Pozzi, Uzen Savas, Eric F Johnson, F Peter Guengerich
Cytochrome P450 (P450, CYP) 4A11 is a human fatty acid ω-hydroxylase that catalyzes the oxidation of arachidonic acid to the eicosanoid 20- hydroxyeicosatetraenoic acid (20-HETE), which plays important roles in regulating blood pressure regulation. Variants of P450 4A11 have been associated with high blood pressure and resistance to anti-hypertensive drugs, and 20-HETE has both pro- and antihypertensive properties relating to increased vasoconstriction and natriuresis, respectively. These physiological activities are likely influenced by the redox environment, but the mechanisms are unclear...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28531339/limtox-a-web-tool-for-applied-text-mining-of-adverse-event-and-toxicity-associations-of-compounds-drugs-and-genes
#5
Andres Cañada, Salvador Capella-Gutierrez, Obdulia Rabal, Julen Oyarzabal, Alfonso Valencia, Martin Krallinger
A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28530704/upregulation-of-cyp17a1-by-sp1-mediated-dna-demethylation-confers-temozolomide-resistance-through-dhea-mediated-protection-in-glioma
#6
J-Y Chuang, W-L Lo, C-Y Ko, S-Y Chou, R-M Chen, K-Y Chang, J-J Hung, W-C Su, W-C Chang, T-I Hsu
Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28529725/the-catalytic-function-of-cytochrome-p450-is-entwined-with-its-membrane-bound-nature
#7
REVIEW
Carlo Barnaba, Katherine Gentry, Nirupama Sumangala, Ayyalusamy Ramamoorthy
Cytochrome P450, a family of monooxygenase enzymes, is organized as a catalytic metabolon, which requires enzymatic partners as well as environmental factors that tune its complex dynamic. P450 and its reducing counterparts-cytochrome P450-reductase and cytochrome b 5 -are membrane-bound proteins located in the cytosolic side of the endoplasmic reticulum. They are believed to dynamically associate to form functional complexes. Increasing experimental evidence signifies the role(s) played by both protein-protein and protein-lipid interactions in P450 catalytic function and efficiency...
2017: F1000Research
https://www.readbyqxmd.com/read/28528513/the-expansive-role-of-oxylipins-on-platelet-biology
#8
REVIEW
Jennifer Yeung, Megan Hawley, Michael Holinstat
In mammals, three major oxygenases, cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450), generate an assortment of unique lipid mediators (oxylipins) from polyunsaturated fatty acids (PUFAs) which exhibit pro- or anti-thrombotic activity. Over the years, novel oxylipins generated from the interplay of theoxygenase activity in various cells, such as the specialized pro-resolving mediators (SPMs), have been identified and investigated in inflammatory disease models. Although platelets have been implicated in inflammation, the role and mechanism of these SPMs produced from immune cells on platelet function are still unclear...
May 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28527918/cytochrome-p450-eicosanoids-in-cerebrovascular-function-and-disease
#9
REVIEW
Catherine M Davis, Xuehong Liu, Nabil J Alkayed
Cytochrome P450 eicosanoids play important roles in brain function and disease through their complementary actions on cell-cell communications within the neurovascular unit (NVU) and mechanisms of brain injury. Epoxy- and hydroxyeicosanoids, respectively formed by cytochrome P450 epoxygenases and ω-hydroxylases, play opposing roles in cerebrovascular function and in pathological processes underlying neural injury, including ischemia, neuroinflammation and oxidative injury. P450 eicosanoids also contribute to cerebrovascular disease risk factors, including hypertension and diabetes...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527914/impact-of-hepatic-p450-mediated-biotransformation-on-the-disposition-and-respiratory-tract-toxicity-of-inhaled-naphthalene
#10
Nataliia Kovalchuk, Jacklyn Kelty, Lei Li, Matthew Hartog, Qing-Yu Zhang, Patricia Edwards, Laura Van Winkle, Xinxin Ding
We determined whether a decrease in hepatic microsomal cytochrome P450 activity would impact lung toxicity induced by inhalation exposure to naphthalene (NA), a ubiquitous environmental pollutant. The liver-Cpr-null (LCN) mouse showed decreases in microsomal metabolism of NA in liver, but not lung, compared to wild-type (WT) mouse. Plasma levels of NA and NA-glutathione conjugates (NA-GSH) were both higher in LCN than in WT mice after a 4-h nose-only NA inhalation exposure at 10ppm. Levels of NA were also higher in lung and liver of LCN, compared to WT, mice, following exposure to NA at 5 or 10ppm...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28527633/anthelmintic-activity-of-cytochrome-p450-inhibitors-miconazole-and-clotrimazole-in-vitro-effect-on-the-liver-fluke-opisthorchis-felineus
#11
Viatcheslav A Mordvinov, Alexander G Shilov, Maria Y Pakharukova
Discovery of drugs for the treatment of opisthorchiasis and schistosomiasis is a high priority. The basic metabolic cytochrome P450 (CYP) system in parasitic flatworms contains a single gene. CYP of the liver fluke Opisthorchis felineus, the causative agent of opisthorchiasis, is important for survival of the worm, so may be a promising target for therapeutics against liver fluke infection. The aims of this study were: (i) to analyse in-vitro anthelmintic activity of various CYP inhibitors using standard motility and mortality assays against juvenile and adult O...
May 17, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28527127/evaluation-of-heparg-cells-for-the-assessment-of-indirect-drug-induced-hepatotoxicity-using-inh-as-a-model-substance
#12
Anika Mann, Thomas Pelz, Knut Rennert, Alexander Mosig, Michael Decker, Amelie Lupp
HepaRG cells are widely used as an in vitro model to assess drug-induced hepatotoxicity. However, only few studies exist so far regarding their suitability to detect the effects of drugs requiring a preceding activation via the cytochrome P450 (CYP) system. A prototypic substance is the anti-tuberculosis agent INH, which is metabolized into N-acetylhydrazine, which then triggers hepatotoxicity. Therefore, the aim of the present study was to test if this effect can also be detected in HepaRG cells and if it can be counteracted by the known hepatoprotectant silibinin...
May 19, 2017: Human Cell
https://www.readbyqxmd.com/read/28526448/the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-uncouple-and-inhibit-the-mitochondrial-respiratory-chain-in-heparg-cells
#13
David Grünig, Andrea Felser, Jamal Bouitbir, Stephan Krähenbühl
The catechol-O-methyltransferase inhibitor tolcapone causes hepatotoxicity and mitochondrial damage in animal models. We studied the interaction of tolcapone with mitochondrial respiration in comparison to entacapone in different experimental models. In HepaRG cells (human cell-line), tolcapone decreased the ATP content (estimated IC50 100±15μM) and was cytotoxic (estimated IC50 333±45μM), whereas entacapone caused no cytotoxicity and no ATP depletion up to 200μM. Cytochrome P450 induction did not increase the toxicity of the compounds...
May 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28525367/liposomal-co-delivered-oleanolic-acid-attenuates-doxorubicin-induced-multi-organ-toxicity-in-hepatocellular-carcinoma
#14
Muhammad Sarfraz, Attia Afzal, Shahid Masood Raza, Sajid Bashir, Asadullah Madni, Muhammad Waseem Khan, Xiang Ma, Guangya Xiang
Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC)...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525288/inference-of-the-genetic-polymorphisms-of-cyp2d6-in-six-subtribes-of-the-malaysian-orang-asli-from-whole-genome-sequencing-data
#15
Choo Yee Yu, Geik Yong Ang, Vinothini Subramaniam, Richard Johari James, Aminuddin Ahmad, Thuhairah Abdul Rahman, Fadzilah Mohd Nor, Syahrul Azlin Shaari, Lay Kek Teh, Mohd Zaki Salleh
AIMS: CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study aims to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli. METHODS: Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing...
May 19, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28525276/chemoenzymatic-total-synthesis-and-structural-diversification-of-tylactone-based-macrolide-antibiotics-through-late-stage-polyketide-assembly-tailoring-and-c-h-functionalization
#16
Andrew N Lowell, Matthew D DeMars, Samuel T Slocum, Fengan Yu, Krithika Anand, Joseph A Chemler, Nisha Korakavi, Jennifer K Priessnitz, Sung Ryeol Park, Aaron A Koch, Pamela J Schultz, David H Sherman
Polyketide synthases (PKSs) represent a powerful catalytic platform capable of effecting multiple carbon-carbon bond forming reactions and oxidation state adjustments. We explored the functionality of two terminal PKS modules that produce the 16-membered tylosin macrocycle, using them as biocatalysts in the chemoenzymatic synthesis of tylactone and its subsequent elaboration to complete the first total synthesis of the juvenimicin, M-4365, and rosamicin classes of macrolide antibiotics via late-stage diversification...
May 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28525267/the-supernatant-from-hepatocyte-cultures-with-drugs-that-cause-idiosyncratic-liver-injury-activates-macrophage-inflammasomes
#17
Ryuji Kato, Jack Uetrecht
There is increasing evidence that most idiosyncratic drug-induced liver injury (IDILI) is immune mediated, and in most cases reactive metabolites appear to be responsible for induction of this immune response. Reactive metabolites can cause cell damage with the release of damage-associated molecular patterns (DAMPs), which is thought to be involved in immune activation. Presumably the reason that the liver is a common target of idiosyncratic drug reactions is because it is the major site of drug metabolism and reactive metabolite formation...
May 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28524079/assembly-of-hepatocyte-spheroids-using-magnetic-3d-cell-culture-for-cyp450-inhibition-induction
#18
Pujan K Desai, Hubert Tseng, Glauco R Souza
There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28523515/distribution-of-exogenous-and-endogenous-cyp3a-markers-and-related-factors-in-healthy-males-and-females
#19
Jieon Lee, Andrew HyoungJin Kim, SoJeong Yi, SeungHwan Lee, Seo Hyun Yoon, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho
Cytochrome P450 (CYP) 3A is an important drug-metabolizing enzyme in humans. Assessing CYP3A activity is necessary for predicting therapeutic outcomes or the potential adverse events of various therapeutics. This study sought to evaluate the distribution of endogenous and exogenous markers reflecting hepatic CYP3A activity and related factors affecting its activity in healthy male and female. Each subject was given a single 1 mg dose of midazolam intravenously. Pharmacokinetics, pharmacometabolomics, and pharmacogenomics analyses were performed to evaluate CYP3A activity...
May 18, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28522909/in-vitro-and-in-vivo-antioxidative-and-hepatoprotective-activity-of-aqueous-extract-of-cortex-dictamni
#20
Lin Li, Yun-Feng Zhou, Yan-Lin Li, Li-Li Wang, Hiderori Arai, Yang Xu
AIM: To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl4)-induced liver damage in rats. METHODS: The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation...
April 28, 2017: World Journal of Gastroenterology: WJG
keyword
keyword
13830
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"