keyword
MENU ▼
Read by QxMD icon Read
search

zileuton

keyword
https://www.readbyqxmd.com/read/28865292/pyrazole-hydrazone-derivatives-as-anti-inflammatory-agents-design-synthesis-biological-evaluation-cox-1-2-5-lox-inhibition-and-docking-study
#1
Mohamed A Abdelgawad, Madlen B Labib, Mahmoud Abdel-Latif
A new series of pyrazole-hydrazone derivatives 4a-i were designed and synthesized, their chemical structures were confirmed by IR, (1)H NMR, (13)C NMR, MS spectral data and elemental analysis. IC50 values for all prepared compounds to inhibit COX-1, COX-2 and 5-LOX enzymes were determined in vitro. Compounds 4a (IC50=0.67μM) and 4b (IC50=0.58μM) showed better COX-2 inhibitory activity than celecoxib (IC50=0.87μM) with selectivity index (SI=8.41, 10.55 in sequent) relative to celecoxib (SI=8.85). Also, compound 4a and 4b exhibited superior inhibitory activity against 5-LOX (IC50=1...
August 30, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28860177/effect-of-zileuton-on-osteoporotic-bone-and-its-healing-expression-of-bone-and-brain-genes-in-rats
#2
Dominik Saul, Milena Ninkovic, Marina Komrakova, Lorenz Wolff, Turab Gasimov, Björn Menger, Daniel Bernd Hoffmann, Veit Rohde, Stephan Sehmisch
Estrogen deficiency and aging are associated with osteoporosis, impaired bone healing and lower cognitive performance. Close functional and physical connections occur between bone and the central nervous system. An anti-inflammatory drug, zileuton, is known to have a positive effect on bone and ischemic brain. We studied the effect of zileuton on bone, its healing and on the genes for bone-brain cross-talks. Three-month-old Sprague-Dawley rats were ovariectomized or left untreated. After 8 weeks, bilateral metaphyseal tibia osteotomy with plate osteosynthesis was performed in all rats...
August 31, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28720504/synthesis-of-novel-hybrids-of-pyrazole-and-coumarin-as-dual-inhibitors-of-cox-2-and-5-lox
#3
Fa-Qian Shen, Zhong-Chang Wang, Song-Yu Wu, Shen-Zhen Ren, Ruo-Jun Man, Bao-Zhong Wang, Hai-Liang Zhu
In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin who was reported to exhibit 5-LOX inhibition to select potent compounds using adequate biological trials sequentially including selective inhibition of COX-2 and 5-LOX, anti-proliferation in vitro, cells apoptosis and cell cycle. Among them, the most potent compound 11g (IC50=0...
August 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28713783/streptococcus-pyogenes-phospholipase-a2-induces-the-expression-of-adhesion-molecules-on-human-umbilical-vein-endothelial-cells-and-aorta-of-mice
#4
Masataka Oda, Hisanori Domon, Mie Kurosawa, Toshihito Isono, Tomoki Maekawa, Masaya Yamaguchi, Shigetada Kawabata, Yutaka Terao
The Streptococcus pyogenes phospholipase A2 (SlaA) gene is highly conserved in the M3 serotype of group A S. pyogenes, which often involves hypervirulent clones. However, the role of SlaA in S. pyogenes pathogenesis is unclear. Herein, we report that SlaA induces the expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) via the arachidonic acid signaling cascade. Notably, recombinant SlaA induced ICAM1 and VCAM1 expression in human umbilical vein endothelial cells (HUVECs), resulting in enhanced adhesion of human monocytic leukemia (THP-1) cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28710425/naja-sputatrix-venom-preconditioning-attenuates-neuroinflammation-in-a-rat-model-of-surgical-brain-injury-via-pla2-5-lox-ltb4-cascade-activation
#5
Yuechun Wang, Prativa Sherchan, Lei Huang, Onat Akyol, Devin W McBride, John H Zhang
Inflammatory preconditioning is a mechanism in which exposure to small doses of inflammatory stimuli prepares the body against future massive insult by activating endogenous protective responses. Phospholipase A2/5-lipoxygenase/leukotriene-B4 (PLA2/5-LOX/LTB4) axis is an important inflammatory signaling pathway. Naja sputatrix (Malayan spitting cobra) venom contains 15% secretory PLA2 of its dry weight. We investigated if Naja sputatrix venom preconditioning (VPC) reduces surgical brain injury (SBI)-induced neuroinflammation via activating PLA2/5-LOX/LTB4 cascade using a partial frontal lobe resection SBI rat model...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694473/5-lo-inhibition-ameliorates-palmitic-acid-induced-er-stress-oxidative-stress-and-insulin-resistance-via-ampk-activation-in-murine-myotubes
#6
Hyun Jeong Kwak, Hye-Eun Choi, Hyae Gyeong Cheon
Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic effects induced by PA...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680195/new-hydroxycinnamic-acid-esters-as-novel-5-lipoxygenase-inhibitors-that-affect-leukotriene-biosynthesis
#7
Luc H Boudreau, Grégoire Lassalle-Claux, Marc Cormier, Sébastien Blanchard, Marco S Doucet, Marc E Surette, Mohamed Touaibia
Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated therapeutic target. As of today, zileuton remains the only clinically approved 5-lipoxygenase inhibitor; however, its use has been limited due to severe side effects in some patients. Hence, the search for a better 5-lipoxygenase inhibitor continues...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28669741/design-synthesis-and-biological-evaluation-of-some-novel-indolizine-derivatives-as-dual-cyclooxygenase-and-lipoxygenase-inhibitor-for-anti-inflammatory-activity
#8
Sushant K Shrivastava, Pavan Srivastava, Robin Bandresh, Prabhash Nath Tripathi, Avanish Tripathi
Some novel indolizine derivatives were synthesized by bioisosteric modification of imidazo[1,2-a]pyridine for anti-inflammatory activity. The physicochemical characterization and structure of compounds were elucidated by state of the art spectroscopic technique. Induced fit docking was performed for initial screening to elucidate the interactions with corresponding amino acids of cyclooxygenase (COX-1, COX-2) and lipoxygenase (LOX) enzymes. The target compounds 53-60 were then evaluated against in vivo carrageenan and arachidonic acid induced rat paw edema models for anti-inflammatory activity...
August 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28623130/leukotriene-signaling-via-alox5-and-cysteinyl-leukotriene-receptor-1-is-dispensable-for-in%C3%A2-vitro-growth-of-cd34-cd38-stem-and-progenitor-cells-in-chronic-myeloid-leukemia
#9
Monika Dolinska, Alexandre Piccini, Wan Man Wong, Eleni Gelali, Anne-Sofie Johansson, Johannis Klang, Pingnan Xiao, Elham Yektaei-Karin, Ulla Olsson Strömberg, Satu Mustjoki, Leif Stenke, Marja Ekblom, Hong Qian
Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) are remarkably effective inducing deep molecular remission in most patients. However, they are less effective to eradicate the leukemic stem cells (LSC), resulting in disease persistence. Therefore, there is great need to develop novel therapeutic strategies to specifically target the LSC. In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28512667/involvement-of-leukotriene-b4-released-from-keratinocytes-in-itch-associated-response-to-intradermal-interleukin-31-in-mice
#10
Tsugunobu Andoh, Ayako Harada, Yasushi Kuraishi
A recent study suggests that interleukin-31 (IL-31) exerts its effect via indirect mechanisms rather than through direct stimulation of cutaneous nerves. However, the underlying peripheral mechanisms of IL-31-induced itch in the skin remain unclear. Therefore, the present study investigated the peripheral mechanisms underlying IL-31-induced itch in mice. IL-31-induced itch-related response was inhibited by anti-allergic drugs (tranilast and azelastine), but not by an H1 histamine receptor antagonist (terfenadine)...
August 31, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28455215/effect-of-the-lipoxygenase-inhibitors-baicalein-and-zileuton-on-the-vertebra-in-ovariectomized-rats
#11
D Saul, S Gleitz, H H Nguyen, R L Kosinsky, S Sehmisch, D B Hoffmann, M Wassmann, B Menger, M Komrakova
Osteoporosis is one of the most common diseases worldwide. In osteoporosis, vertebral fractures represent a major burden. Lipoxygenase (LOX) inhibitors such as baicalein and zileuton may represent a promising therapeutic option owing to their antioxidative effects and suppression of various inflammatory processes in muscle and bone. The effect of these LOX inhibitors on the spine was studied in osteopenic rats. Female Sprague-Dawley rats were divided two times into five groups: four groups each were ovariectomized (OVX) and one control group was non-ovariectomized (NON-OVX)...
April 26, 2017: Bone
https://www.readbyqxmd.com/read/28388737/lack-of-long-term-neurologic-efficacy-of-zileuton-in-sj%C3%A3-gren-larsson-s-syndrome
#12
Catherine Sarret, Samia Pichard, Alexandra Afenjar, Odile Boespflug-Tanguy
No abstract text is available yet for this article.
April 7, 2017: Neuropediatrics
https://www.readbyqxmd.com/read/28383037/five-lipoxygenase-hypomethylation-mediates-the-homocysteine-effect-on-alzheimer-s-phenotype
#13
Jian-Guo Li, Carlos Barrero, Salim Merali, Domenico Praticò
Environmental and genetic risk factors are implicated in the pathogenesis of Alzheimer's disease (AD). However, how they interact and influence its pathogenesis remains to be investigated. High level of homocysteine (Hcy) is an AD risk factor and associates with an up-regulation of the ALOX5 gene. In the current paper we investigated whether this activation is responsible for the Hcy effect on the AD phenotype and the mechanisms involved. Triple transgenic mice were randomized to receive regular chow diet, a diet deficient in folate and B vitamins (Diet), which results in high Hcy, or the Diet plus zileuton, a specific ALOX5 inhibitor, for 7 months...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344594/articular-inflammation-induced-by-an-enzymatically-inactive-lys49-phospholipase-a2-activation-of-endogenous-phospholipases-contributes-to-the-pronociceptive-effect
#14
Renata Gonçalves Dias, Sandra Coccuzzo Sampaio, Morena Brazil Sant'Anna, Fernando Queiroz Cunha, José María Gutiérrez, Bruno Lomonte, Yara Cury, Gisele Picolo
BACKGROUND: Arthritis is a set of inflammatory conditions that induce aching, stiffness, swelling, pain and may cause functional disability with severe consequences to the patient's lives. These are multi-mediated pathologies that cannot be effectively protected and/or treated. Therefore, the aim of this study was to establish a new model of acute arthritis, using a Lys49-PLA2 (Bothrops asper myotoxin II; MT-II) to induce articular inflammation. METHODS: The articular inflammation was induced by MT-II (10 μg/joint) injection into the left tibio-tarsal or femoral-tibial-patellar joints...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28240894/evaluation-of-dual-5-lipoxygenase-microsomal-prostaglandin-e2-synthase-1-inhibitory-effect-of-natural-and-synthetic-acronychia-type-isoprenylated-acetophenones
#15
Alexandra Svouraki, Ulrike Garscha, Eirini Kouloura, Simona Pace, Carlo Pergola, Verena Krauth, Antonietta Rossi, Lidia Sautebin, Maria Halabalaki, Oliver Werz, Nicolas Gaboriaud-Kolar, Alexios-Leandros Skaltsounis
Among the pathways responsible for the development of inflammatory responses, the cyclooxygenase and lipoxygenase pathways are among the most important ones. Two key enzymes, namely, 5-LO and mPGES-1, are involved in the biosynthesis of leukotrienes and prostaglandins, respectively, which are considered attractive therapeutic targets, so their dual inhibition might be an effective strategy to control inflammatory deregulation. Several natural products have been identified as 5-LO inhibitors, with some also being dual 5-LO/mPGES-1 inhibitors...
March 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28132911/effect-of-alpha-lipoic-acid-on-leukotriene-a4-hydrolase
#16
María José Torres, Angélica Fierro, C David Pessoa-Mahana, Javier Romero-Parra, Gonzalo Cabrera, Mario Faúndez
Leukotriene A4 hydrolase is a soluble enzyme with epoxide hydrolase and aminopeptidase activities catalysing the conversion of leukotriene A4 to leukotriene B4 and the hydrolysis of the peptide proline-glycine-proline. Imbalances in leukotriene B4 synthesis are related to several pathologic conditions. Currently there are no available drugs capable to modulate the synthesis of leukotriene B4 or to block its receptors. Here we show the inhibitory profile of alpha lipoic acid on the activity of leukotriene A4 Hydrolase...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28089919/an-orally-active-geranyl-acetophenone-attenuates-airway-remodeling-in-a-murine-model-of-chronic-asthma
#17
Yu Zhao Lee, Khozirah Shaari, Manraj Singh Cheema, Chau Ling Tham, Mohd Roslan Sulaiman, Daud Ahmad Israf
2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a synthetic compound that is naturally found in Melicope ptelefolia. We had previously demonstrated that parenteral administration of tHGA reduces pulmonary inflammation in OVA-sensitized mice. In this study, we evaluated the effect of orally administered tHGA upon airway remodeling in a murine model of chronic asthma. Female BALB/C mice were sensitized intraperitoneally with ovalbumin (OVA) on day 0, 7 and 14, followed by aerosolized 1% OVA 3 times per week for 6 weeks...
February 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28035009/inhibition-of-leukotriene-b4-action-mitigates-intracerebral-hemorrhage-associated-pathological-events-in-mice
#18
Masanori Hijioka, Junpei Anan, Hayato Ishibashi, Yuki Kurauchi, Akinori Hisatsune, Takahiro Seki, Tomoaki Koga, Takehiko Yokomizo, Takao Shimizu, Hiroshi Katsuki
Infiltration of neutrophils has been suggested to play an important role in the pathogenesis of intracerebral hemorrhage (ICH) for which effective therapeutic interventions remain unavailable. In the present study we focused on leukotriene B4 (LTB4) as a potent chemotactic factor for neutrophils in order to address its contribution to the pathologic events associated with ICH. ICH with hematoma expansion into the internal capsule that resulted in severe sensorimotor dysfunction was induced by injection of collagenase in mouse striatum...
March 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27849187/inhibition-of-5-lipoxygenase-by-zileuton-in-a-rat-model-of-myocardial-infarction
#19
Leyla Abueid, Ünal Uslu, Alev Cumbul, Ayliz Velioğlu Öğünç, Feriha Ercan, İnci Alican
OBJECTIVE: The goal of the present study was to investigate the effects of 5-lipoxygenase (5-LOX) inhibition, alone and with cyclooxygenase (COX) inhibitors, on inflammatory parameters and apoptosis in ischemia/reperfusion (I/R)-induced myocardial damage in rats. For this purpose, zileuton, a selective and potent inhibitor of 5-LOX, resulting in suppression leukotriene production, was used. METHODS: Male Wistar rats (200-250 g; n=12 per group) were used in the study...
April 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/27836196/optimization-of-benzoquinone-and-hydroquinone-derivatives-as-potent-inhibitors-of-human-5-lipoxygenase
#20
Antonella Peduto, Maria Scuotto, Verena Krauth, Fiorentina Roviezzo, Antonietta Rossi, Veronika Temml, Veronica Esposito, Hermann Stuppner, Daniela Schuster, Bruno D'Agostino, Chiara Schiraldi, Mario de Rosa, Oliver Werz, Rosanna Filosa
Aiming to assess the biological activities of synthetic 1,4-benzoquinones, we previously synthesized different libraries of benzoquinones with lipophilic and bulky alkyl- or aryl-substituents that inhibited 5-lipoxygenase (5-LO). The high potency of 4,5-dimethoxy-3-alkyl-1,2-benzoquinones on 5-LO led to the idea to further modify the structures and thus to improve the inhibitory potential in vitro and in vivo as well as to investigate SARs. Systematic structural optimization through accurate structure-based design resulted in compound 30 (3-tridecyl-4,5-dimethoxybenzene-1,2-diol), an ubiquinol derivative that exhibited the strongest anti-inflammatory effect, with a 10-fold improved 5-LO inhibitory activity (IC50 = 28 nM) in activated neutrophils...
February 15, 2017: European Journal of Medicinal Chemistry
keyword
keyword
70058
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"