A novel COX-2 inhibitor pyrazole derivative proven effective as an anti-inflammatory and analgesic drug.

Abstract:

:The introduction of new COX-2 inhibitors with high efficacy and enhanced safety profile would be a great achievement in the development of anti-inflammatory drugs. This study was designed to screen and assess the anti-inflammatory and analgesic activities as well as some of the expected side effects of some pyrazole derivatives, newly synthesized as potential COX-2 inhibitors at the Faculty of Pharmacy, Alexandria University and compared to indomethacin and celecoxib. Twelve compounds were screened for their anti-inflammatory activity using carrageenan-induced paw oedema and cotton pellet granuloma tests. On the basis of their apparent anti-inflammatory activity, four compounds with different substitutions were selected for the evaluation of their analgesic activity using the formalin-induced hyperalgesia and hot-plate tests. Compound AD 532, ((4-(3-(4-Methylphenyl)-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide)), showed very promising results. In the single-dose and subchronic toxicity studies, compound AD 532 showed no ulcerogenic effect and produced minimal effects on renal function. Furthermore, compound AD 532 was a less potent inhibitor of COX-2 in vitro than celecoxib, which may indicate lower potential cardiovascular toxicity. It is concluded that compound AD 532 appears to be a promising and safe option for the management of chronic inflammatory conditions. This study recommends more in-depth investigation into the therapeutic effects and toxicity profile of this compound including its cardiovascular toxicity.

authors

Mohy El-Din MM,Senbel AM,Bistawroos AA,El-Mallah A,Nour El-Din NA,Bekhit AA,Abd El Razik HA

doi

10.1111/j.1742-7843.2010.00648.x

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

263-73

issue

4

eissn

1742-7835

issn

1742-7843

journal_volume

108

pub_type

杂志文章
  • Post-Injection Delirium/Sedation Syndrome after Olanzapine Long-Acting Intramuscular Injection - Who is at Risk?

    abstract::The post-injection olanzapine delirium/sedation syndrome (PDSS) was observed in a 60-year-old Caucasian, schizophrenic, non-smoker and underweight [body mass index (BMI), 18.2 kg/m(2) ] women after the fourth intramuscular injection of 405 mg olanzapine pamoate. Clinical symptoms of PDSS were similar to those of acute...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12394

    authors: Łukasik-Głębocka M,Sommerfeld K,Teżyk A,Panieński P,Żaba C,Zielińska-Psuja B

    更新日期:2015-09-01 00:00:00

  • The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism.

    abstract::Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1742-7843.2009.00378.x

    authors: Zwisler ST,Enggaard TP,Noehr-Jensen L,Pedersen RS,Mikkelsen S,Nielsen F,Brosen K,Sindrup SH

    更新日期:2009-04-01 00:00:00

  • Effect of betulinic acid on anticancer drug-resistant colon cancer cells.

    abstract::Primary or acquired resistance of tumours to established chemotherapeutic regimens is a major concern in oncology. Attempts to improve the survival of cancer patients largely depend on strategies to prevent tumour cell resistance. 5-Fluorouracil (5-FU)-based chemotherapy with a combination of other drugs such as irino...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2007.00115.x

    authors: Jung GR,Kim KJ,Choi CH,Lee TB,Han SI,Han HK,Lim SC

    更新日期:2007-10-01 00:00:00

  • In situ study of the effect of naringin, talinolol and protein-energy undernutrition on intestinal absorption of saquinavir in rats.

    abstract::To study the potential interactions of naringin (NAR), talinolol (TAL) and protein-energy undernutrition (PEU) in the absorption process of saquinavir (SQV), perfusion experiments were performed in the small intestine of rats at different SQV concentrations. The results obtained demonstrated that SQV intestinal absorp...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2011.00714.x

    authors: Catalán-Latorre A,Nácher A,Merino V,Jiménez-Torres NV,Merino-Sanjuán M

    更新日期:2011-10-01 00:00:00

  • The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction.

    abstract::Sudden death due to acute intoxication occurs frequently in patients with opioid addiction (OA). To examine whether certain genotypes were associated with this, we examined the frequencies of 29 SNPs located in candidate genes related to opioid pharmacology: ABCB1, OPRM1, UGT2B7, CYP3A5, CYP2B6, CYP2C19, CYP2D6, COMT,...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12602

    authors: Christoffersen DJ,Damkier P,Feddersen S,Möller S,Thomsen JL,Brasch-Andersen C,Brøsen K

    更新日期:2016-10-01 00:00:00

  • Prolonged antispasmodic effect in isolated radial artery graft and pronounced platelet inhibition induced by the inodilator drug, levosimendan.

    abstract::Radial artery frequently develops spasm and requires vasodilator therapy during coronary artery bypass graft surgery (CABG). Levosimendan was recently shown to oppose 5-hydroxytryptamine-induced contraction of radial artery (RA) grafts. The aim of the present study was to explore whether levosimendan retains its vasod...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2011.00801.x

    authors: Ambrus N,Szolnoky J,Pollesello P,Kun A,Varró A,Papp JG,Pataricza J

    更新日期:2012-03-01 00:00:00

  • Effects of methylated derivatives of Luteolin isolated from Cyperus alopecuroides in rat H4IIE hepatoma cells*.

    abstract::Polyphenols are ubiquitous substances in human diet. Their antioxidative, antiinflammatory and antiviral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. Luteolin is metabolized to glucuronides, but also to methylated derivatives. For examp...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2006.pto_300.x

    authors: Michels G,Mohamed GA,Weber N,Chovolou Y,Kampkötter A,Wätjen W,Proksch P

    更新日期:2006-02-01 00:00:00

  • A review of the Ghana National Health Insurance Scheme claims database: possibilities and limits for drug utilization research.

    abstract:BACKGROUND:There are inadequate data on prescribed drug utilization in Sub-Saharan Africa (SSA). Drug utilization research (DUR) in this region is hampered by lack of access to databases that capture prescribed drug utilization such as health insurance claims, electronic medical records and disease registries. The prim...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/bcpt.13136

    authors: Ankrah D,Hallas J,Odei J,Asenso-Boadi F,Dsane-Selby L,Donneyong M

    更新日期:2019-01-01 00:00:00

  • Applying concepts of generalizability theory on data from experimental pain studies to investigate reliability.

    abstract::This work demonstrates how full modelling power in statistically mixed models can be used to study generalizability (reliability) coefficients of advanced data from human experimental pain studies utilizing placebo data from drug screening trials. This can be used to help optimizing outcome parameters from existing da...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1742-7843.2009.00408.x

    authors: Pryseley A,Ledent EY,Drewes AM,Staahl C,Olesen AE,Arendt-Nielsen L

    更新日期:2009-08-01 00:00:00

  • Anticonvulsant and behavioural effects of the denatured venom of the social wasp Polybia occidentalis (Polistinae, Vespidae).

    abstract::Several investigations demonstrate that neurotoxins isolated from venoms of spiders and wasps may exert specific and selective activity on structures of the mammalian CNS. In the present work we examine the neurological effects of the low molecular weight compounds of the denatured venom of the neotropical social wasp...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2005.pto_137.x

    authors: Mortari MR,Cunha AO,de Oliveira L,Vieira EB,Gelfuso EA,Coutinho-Netto J,Ferreira dos Santos W

    更新日期:2005-11-01 00:00:00

  • Naringin inhibits ROS-activated MAPK pathway in high glucose-induced injuries in H9c2 cardiac cells.

    abstract::Naringin, an active flavonoid isolated from citrus fruit extracts, exhibits biological and pharmacological properties, such as antioxidant activity and antidiabetic effect. Mitogen-activated protein kinase (MAPK) signalling pathway has been shown to participate in hyperglycaemia-induced injury. The present study teste...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12153

    authors: Chen J,Guo R,Yan H,Tian L,You Q,Li S,Huang R,Wu K

    更新日期:2014-04-01 00:00:00

  • Sodium Nitrite Prevents both Reductions in Circulating Nitric Oxide and Hypertension in 7-Day Lead-Treated Rats.

    abstract::Hypotensive effects of oral sodium nitrite have been reported as alternative sources of nitric oxide (NO) formation in animals and human beings. Reductions in NO bioavailability were observed in lead-induced hypertension. However, no previous study has examined whether a single daily dose of sodium nitrite prevents th...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12480

    authors: Gonçalves-Rizzi VH,Nascimento RA,Possomato-Vieira JS,Dias-Junior CA

    更新日期:2016-03-01 00:00:00

  • Educating European (junior) doctors for safe prescribing.

    abstract::Evidence of poor prescribing is widespread including overuse of medicines, underuse of effective medicines, avoidable adverse drug reactions and medication errors. Junior doctors who have recently graduated are responsible for much of the prescribing that takes place in hospitals and are implicated in many of the adve...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type:

    doi:10.1111/j.1742-7843.2007.00141.x

    authors: Maxwell SR,Cascorbi I,Orme M,Webb DJ,Joint BPS\/EACPT Working Group on Safe Prescribing.

    更新日期:2007-12-01 00:00:00

  • In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by L-cysteine.

    abstract::This study was undertaken in order to investigate a) the short- and long-term in vivo effects of cadmium (Cd) on brain acetylcholinesterase (AChE), (Na+, K+)-ATPase activities in adult rats, b) the concentration-dependent in vitro and in vivo (acute experiment) effects of Cd on the activity of those enzymes, c) the in...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2004.pto940303.x

    authors: Carageorgiou H,Tzotzes V,Pantos C,Mourouzis C,Zarros A,Tsakiris S

    更新日期:2004-03-01 00:00:00

  • Effect of Desmopressin on the Amount of Bleeding and Transfusion Requirements in Patients Undergoing Heart Transplant Surgery.

    abstract::One of the most common risks after a heart transplant is bleeding. In this study, the effect of desmopressin administration on the amount of bleeding and transfusion requirements after heart transplant surgery was investigated. In a double-blind clinical trial, 48 patients who were candidates for heart transplant surg...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcpt.12780

    authors: Jahangirifard A,Razavi MR,Ahmadi ZH,Forozeshfard M

    更新日期:2017-09-01 00:00:00

  • Development of a Robust Mammalian Cell-based Assay for Studying Recombinant α4 β1/3 δ GABAA Receptor Subtypes.

    abstract::δ-Containing GABAA receptors are located extrasynaptically and mediate tonic inhibition. Their involvement in brain physiology positions them as interesting drug targets. There is thus a continued interest in establishing reliable recombinant expression systems for δ-containing GABAA receptors. Inconveniently, the rec...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12778

    authors: Falk-Petersen CB,Søgaard R,Madsen KL,Klein AB,Frølund B,Wellendorph P

    更新日期:2017-08-01 00:00:00

  • Modelling of drug disposition kinetics in in vitro intestinal absorption cell models.

    abstract::One major prerequisite for an orally administered drug is the ability to cross the intestinal epithelia from intestinal lumen into the blood circulation. Therefore, the absorption potential of molecules is studied early on during the drug development process. Permeation experiments using cultured cell monolayers are o...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2009.00504.x

    authors: Heikkinen AT,Korjamo T,Mönkkönen J

    更新日期:2010-03-01 00:00:00

  • Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats.

    abstract::The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days signific...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2007.00005.x

    authors: Farombi EO,Abarikwu SO,Adedara IA,Oyeyemi MO

    更新日期:2007-01-01 00:00:00

  • Structural adaptation of normal and tumour vascular networks.

    abstract::Vascular networks are dynamic structures, adapting to changing conditions by structural remodelling of vessel diameters and by growth of new vessels and regression of existing vessels. The vast number of blood vessels in the circulatory system, more than 10⁹, implies that vessels' arrangement and structure are not und...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2011.00815.x

    authors: Secomb TW,Dewhirst MW,Pries AR

    更新日期:2012-01-01 00:00:00

  • Human BJ Fibroblasts is an Alternative to Mouse BALB/c 3T3 Cells in In Vitro Neutral Red Uptake Assay.

    abstract::The OECD GD 129 BALB/c 3T3 neutral red uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12790

    authors: Mannerström M,Toimela T,Sarkanen JR,Heinonen T

    更新日期:2017-09-01 00:00:00

  • Effects of the CYP2C9*1/*13 genotype on the pharmacokinetics of lornoxicam.

    abstract::Lornoxicam is extensively metabolized by CYP2C9, and a CYP2C9*13 is one of the principal variant alleles in East Asian populations. The aim of this study was to evaluate the effects of CYP2C9*1/*13 on the pharmacokinetic parameters of lornoxicam in healthy individuals. A single oral dose of 8 mg lornoxicam was given t...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1742-7843.2011.00751.x

    authors: Choi CI,Kim MJ,Jang CG,Park YS,Bae JW,Lee SY

    更新日期:2011-12-01 00:00:00

  • Sulphated polysaccharides: new insight in the prevention of cyclosporine A-induced glomerular injury.

    abstract::The scope of the current study was to examine the possible effects of sulphated polysaccharides against cyclosporine A-induced glomerular injury. Nephrotoxicity induced by cyclosporine A continues to be a major problem despite its potent immunosuppressive action. Adult male albino rats of Wistar strain were categorize...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2007.00081.x

    authors: Josephine A,Veena CK,Amudha G,Preetha SP,Sundarapandian R,Varalakshmi P

    更新日期:2007-07-01 00:00:00

  • Dissection of the Effects of Quercetin on Mouse Myocardium.

    abstract::Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an i...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12743

    authors: Santos MS,Oliveira ED,Santos-Miranda A,Cruz JS,Gondim ANS,Menezes-Filho JER,Souza DS,Pinho-da-Silva L,Jesus ICG,Roman-Campos D,Guatimosim S,Lara A,Conde-Garcia EA,Vasconcelos CML

    更新日期:2017-06-01 00:00:00

  • Plasma levels of 25-hydroxyvitamin D3 and in vivo markers of cytochrome P450 3A activity in Swedes and Koreans: effects of a genetic polymorphism and oral contraceptives.

    abstract::In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25-hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Swe...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12230

    authors: Nylén H,Björkhem-Bergman L,Ekström L,Roh HK,Bertilsson L,Eliasson E,Lindh JD,Diczfalusy U

    更新日期:2014-10-01 00:00:00

  • Cytotoxic and DNA-damaging effects of diterpenoid quinones from the roots of Salvia officinalis L. on colonic and hepatic human cells cultured in vitro.

    abstract::Three diterpenoid quinones (royleanone- SAR 3, horminone- SAR 26, and acetyl horminone- SAR 43) isolated from the roots of Salvia officinalis L. were tested for their cytotoxic and DNA-damaging activity in human colon carcinoma cells Caco-2 and human hepatoma cells HepG2 cultured in vitro. Cytotoxicity was measured by...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2004.pto940605.x

    authors: Slamenová D,Masterová I,Lábaj J,Horváthová E,Kubala P,Jakubíková J,Wsólová L

    更新日期:2004-06-01 00:00:00

  • Polyfluorinated alkyl phosphate ester surfactants - current knowledge and knowledge gaps.

    abstract::Fluorochemicals are a diverse group of synthetically produced compounds with the unique ability to repel water as well as oil. This property makes them ideal for multiple purposes in a variety of consumer and industrial products. Fluorochemicals have been detected in the environment, as well as in human blood, urine a...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/bcpt.12208

    authors: Taxvig C,Rosenmai AK,Vinggaard AM

    更新日期:2014-07-01 00:00:00

  • A Critical Note on Treatment of a Severe Diltiazem Intoxication: High-Dose Calcium and Glucagon Infusions.

    abstract::The morbidity and mortality of a severe calcium channel blocker intoxication is high due to serious toxic cardiac effects. Its treatment is supported by low-quality evidence from the heterogeneous literature. We describe a case of a severe diltiazem intoxication and critically appraise the efficacy and role of high-do...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type:

    doi:10.1111/bcpt.12809

    authors: Van Veggel M,Van der Veen G,Jansen T,Westerman E

    更新日期:2017-11-01 00:00:00

  • In vitro anti-tumour activities of quinolizidine alkaloids derived from Sophora flavescens Ait.

    abstract::The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main active constituents. Here, we report that among the six characterized SF-derived quinolizidine alkaloids including sophoridine...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2010.00653.x

    authors: Lin Z,Huang CF,Liu XS,Jiang J

    更新日期:2011-05-01 00:00:00

  • Genetically engineered animals in drug discovery and development: a maturing resource for toxicologic research.

    abstract::Genetically engineered mice that either over-express a foreign gene (transgenic) or in which the activity of a specific gene has been removed ("knock-out") or replaced ("knock-in") will be used increasingly to investigate molecular mechanisms of disease, to evaluate innovative therapeutic targets, and to screen novel ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2004.pto950402.x

    authors: Bolon B

    更新日期:2004-10-01 00:00:00

  • Atomoxetine increases histamine release and improves learning deficits in an animal model of attention-deficit hyperactivity disorder: the spontaneously hypertensive rat.

    abstract::Substantial development in the pharmacological treatment for attention-deficit hyperactivity disorder (ADHD) has been made recently including approval of new non-stimulant agents targeting noradrenergic, histaminergic and dopaminergic systems. Among such, atomoxetine has been widely used, although its mechanism of act...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2008.00230.x

    authors: Liu LL,Yang J,Lei GF,Wang GJ,Wang YW,Sun RP

    更新日期:2008-06-01 00:00:00