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


: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.


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




Has Abstract


2011-04-01 00:00:00












  • Natural oils affect the human skin integrity and the percutaneous penetration of benzoic acid dose-dependently.

    abstract::Natural oils are extensively used in cosmetics and as treatment for a growing number of more or less specific ailments. Skin irritation and cases of allergy have repeatedly been described in the literature following exposure to these oils. The present study evaluated the extent to which three natural oils (eucalyptus ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Nielsen JB

    更新日期:2006-06-01 00:00:00

  • Induced DNA damage by dental resin monomers in somatic cells.

    abstract::The present in vivo study investigated the genotoxicity of four dental resin monomers: triethyleneglycoldimethacrylate (TEGDMA), hydroxyethylmethacrylate (HEMA), urethanedimethacrylate (UDMA) and bisphenol A-glycidylmethacrylate (BisGMA). The Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster w...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Arossi GA,Lehmann M,Dihl RR,Reguly ML,de Andrade HH

    更新日期:2010-02-01 00:00:00

  • Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR-204 expression.

    abstract::Gastric carcinoma (GC) is a pernicious neoplasm with high morbidity and mortality. Sinomenine (SIN) has long been exploited to heal rheumatoid arthritis. Recently, SIN has been discovered to exert the antitumour functions in diverse cancers. However, the impacts of SIN on GC remain indistinct. We attempted to expose t...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,收录出版


    authors: Yuan H,Zhang J,Li F,Li W,Wang H

    更新日期:2019-11-01 00:00:00

  • Antimetastatic effects of licochalcone B on human bladder carcinoma T24 by inhibition of matrix metalloproteinases-9 and NF-кB activity.

    abstract::This study investigated the mechanisms by which licochalcone B (LCB) inhibits the adhesion,invasion and metastasis of human malignant bladder cancer T24 cells. Cell viability was evaluated using a sulforhodamine B (SRB) assay. Cell migration and invasion ability were conducted using wound-healing assay and matrigel tr...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Zhao H,Yuan X,Jiang J,Wang P,Sun X,Wang D,Zheng Q

    更新日期:2014-12-01 00:00:00

  • Eudesmol isomers induce caspase-mediated apoptosis in human hepatocellular carcinoma HepG2 cells.

    abstract::Eudesmols are naturally occurring sesquiterpenoid alcohols that present cytotoxic effect to cancer cells. Herein, all eudesmol isomers displayed cytotoxicity to different tumour cell lines. α-Eudesmol showed IC₅₀ values ranging from 5.38 ± 1.10 to 10.60 ± 1.33 μg/mL for B16-F10 and K562 cell lines, β-eudesmol showed I...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Bomfim DS,Ferraz RP,Carvalho NC,Soares MB,Pinheiro ML,Costa EV,Bezerra DP

    更新日期:2013-11-01 00:00:00

  • In vitro studies investigating the interactions between degarelix, a decapeptide gonadotropin-releasing hormone blocker, and cytochrome P450.

    abstract::The decapeptide degarelix is a novel competitive gonadotropin-releasing hormone receptor antagonist that has been approved for the treatment of advanced prostate cancer by the FDA and the EU authorities. In this study, the interaction of degarelix with human cytochrome P450 (CYP450) enzymes was investigated in vitro. ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Sonesson A,Rasmussen BB

    更新日期:2011-09-01 00:00:00

  • Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A Nationwide Study in the Netherlands.

    abstract::Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the under-reporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in pharmacovigilance, by as...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Schutte T,Tichelaar J,Reumerman MO,van Eekeren R,Rissmann R,Kramers C,Richir MC,van Puijenbroek EP,van Agtmael MA,Education Committee\/Working Group Research in Education of the Dutch Society of Clinical Pharmacology and Biopharmacy (N

    更新日期:2017-05-01 00:00:00

  • Proteomics: recent applications and new technologies.

    abstract::Interest in proteomics as a tool for drug development and a myriad of other applications continues to expand at a rapid rate. Proteomic analyses have recently been conducted on tissues, biofluids, subcellular components and enzymatic pathways as well as various disease and toxicological states, in both animal models a...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审


    authors: Elrick MM,Walgren JL,Mitchell MD,Thompson DC

    更新日期:2006-05-01 00:00:00

  • The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers.

    abstract::This study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty-three healthy, Danish, Caucasian volunteers representing different pre-defined genotypes each received 10 mg of enalapril. At specified time-points, plasma concentrations of enalapril a...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 临床试验,杂志文章


    authors: Stage C,Jürgens G,Guski LS,Thomsen R,Bjerre D,Ferrero-Miliani L,Lyauk YK,Rasmussen HB,Dalhoff K,INDICES Consortium (for members of this consortium-see Supplementum).

    更新日期:2017-12-01 00:00:00

  • An antithrombotic agent, NQ301, inhibits thromboxane A2 receptor and synthase activity in rabbit platelets.

    abstract::In previous studies we have reported that NQ301, a synthetic 1,4-naphthoquinone derivative, displays a potent antithrombotic activity, and that this might be due to antiplatelet effect, which was mediated by the inhibition of cytosolic Ca(2+) mobilization in activated platelets. In the present study, the effect of NQ3...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Jin YR,Cho MR,Lee KS,Lee JJ,Lim Y,Han XH,Oh KW,Hong JT,Yoo HS,Yun YP

    更新日期:2005-09-01 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


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

    更新日期:2017-08-01 00:00:00

  • Flaws in design, execution and interpretation limit CLARITY-BPA's value for risk assessments of bisphenol A.

    abstract::The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) involved the Food and Drug Administration, the National Toxicology Program and 14 academic investigators funded by the National Institute of Environmental Health Sciences. Two key questions to be answered by CLARITY-BPA were as follo...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审


    authors: Vom Saal FS

    更新日期:2019-08-01 00:00:00

  • Effects of Genetic Variants on Carboxylesterase 1 Gene Expression, and Clopidogrel Pharmacokinetics and Antiplatelet Effects.

    abstract::Several single nucleotide variations (SNVs) affect carboxylesterase 1 (CES1) activity, but the effects of genetic variants on CES1 gene expression have not been systematically investigated. Therefore, our aim was to investigate effects of genetic variants on CES1 gene expression in two independent whole blood sample c...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Neuvonen M,Tarkiainen EK,Tornio A,Hirvensalo P,Tapaninen T,Paile-Hyvärinen M,Itkonen MK,Holmberg MT,Kärjä V,Männistö VT,Neuvonen PJ,Pihlajamäki J,Backman JT,Niemi M

    更新日期:2018-03-01 00:00:00

  • Red Blood cell IMPDH activity in adults and children with or without azathioprine: Relationship between thiopurine metabolites, ITPA and TPMT activities.

    abstract::Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6-thioguanine nucleotides (6-TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as fo...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Citterio-Quentin A,El Mahmoudi A,Perret T,Conway A,Ryan A,Beringer A,Lachaux A,Boulieu R

    更新日期:2019-05-01 00:00:00

  • Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats.

    abstract::Type 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusiv...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Bortolin RH,Freire Neto FP,Arcaro CA,Bezerra JF,da Silva FS,Ururahy MA,Souza KS,Lima VM,Luchessi AD,Lima FP,Lia Fook MV,da Silva BJ,Almeida MD,Abreu BJ,de Rezende LA,de Rezende AA

    更新日期:2017-03-01 00:00:00

  • Direct Inhibitory Effects of Carbon Monoxide on Six Venoms Containing Fibrinogenolytic Metalloproteinases.

    abstract::Since the introduction of antivenom administration over a century ago to treat venomous snake bite, it has been the most effective therapy for saving life and limb. However, this treatment is not always effective and not without potential life-threatening side effects. We tested a new paradigm to abrogate the plasmati...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Nielsen VG,Losada PA

    更新日期:2017-02-01 00:00:00

  • Inhibition of voltage-sensitive sodium channels by the cannabinoid 1 receptor antagonist AM 251 in mammalian brain.

    abstract::The cannabinoid 1 receptor antagonist AM 251 is known to block the inhibitory effects of endocannabinoids and synthetic cannabinoid agonists on transmitter release through an action at presynaptic cannabinoid 1 receptors in brain. We examined the ability of AM 251 to inhibit sodium channel-dependent functions and the ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Liao C,Zheng J,David LS,Nicholson RA

    更新日期:2004-02-01 00:00:00

  • Muscarinic receptors in energy homeostasis: Physiology and pharmacology.

    abstract::Despite increased awareness and intensified biomedical research efforts, the prevalence of obesity continues to rise worldwide. This is alarming, because obesity accelerates the progression of several chronic disorders, including type 2 diabetes, cancer and cardiovascular disease. Individuals who experience significan...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审


    authors: Falk S,Lund C,Clemmensen C

    更新日期:2020-06-01 00:00:00

  • Antinociceptive activity of a new benzofuranone derived from a chalcone.

    abstract::Chalcones represent an important group of natural or synthetic compounds with a variety of biological activities including antinociceptive and anti-inflammatory ones. The aim of this work was the synthesis of a new benzofuranone compound and evaluation of its antinociceptive potential in mice. The new benzofuranone 4 ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Padaratz P,Fracasso M,de Campos-Buzzi F,Corrêa R,Niero R,Delle Monache F,Cechinel-Filho V

    更新日期:2009-10-01 00:00:00

  • Up-regulation of miR-21 and miR-23a Contributes to As2 O3 -induced hERG Channel Deficiency.

    abstract::Arsenic trioxide (As2O3) is used to treat acute pro-myelocytic leukaemia. However, the cardiotoxicity of long QT syndrome restricts its clinical application. Previous studies showed that As2O3 can damage the hERG current via disturbing its trafficking to cellular membrane. Consistent with these findings, in this study...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Zhao X,Shi YQ,Yan CC,Feng PF,Wang X,Zhang R,Zhang X,Li BX

    更新日期:2015-06-01 00:00:00

  • The effect of aggressive rosuvastatin treatment on steroid hormone production in men with coronary artery disease.

    abstract::Most steroid hormones are produced from cholesterol contained in low-density lipoproteins, which is uptaken by the gonads and adrenal cortex, and used as a substrate for steroidogenesis. Theoretically, in states associated with very low-density lipoprotein (LDL) cholesterol levels, cholesterol conversion to steroid ho...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Krysiak R,Okopien B

    更新日期:2014-04-01 00:00:00

  • The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model - A Randomized, Placebo-controlled Trial.

    abstract::Pain involves responses in which both peripheral and central mechanisms contribute to the generation of pain. Pre-clinical laboratory data have supported that a topical formulation of combined diclofenac and methadone (Diclometh) may alleviate local pain, and potentially, the side effect profile should be low. We hypo...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验


    authors: Larsen IM,Drewes AM,Olesen AE

    更新日期:2018-08-01 00:00:00

  • Kolaviron, a natural antioxidant and anti-inflammatory phytochemical prevents dextran sulphate sodium-induced colitis in rats.

    abstract::The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed mainly to its antioxidant and anti-inflammatory effects. This study investigated these effects on dextran sulphate sodium (DSS)-induced ulcerative colitis in rats. Sulfasalazine served as standard reference...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Farombi EO,Adedara IA,Ajayi BO,Ayepola OR,Egbeme EE

    更新日期:2013-07-01 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


    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

  • Pharmacokinetic-pharmacodynamic modelling of biomarker response to sitagliptin in healthy volunteers.

    abstract::Pharmacokinetic/pharmacodynamic (PK/PD) models can be useful tools in new drug development and also optimal drug therapy in patients. This study was designed to develop a PK/PD model of sitagliptin based on the physiology of incretin. The PK/PD data included information derived from two different studies. Study 1 was ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Kim BH,Kim SE,Kang D,Lim KS,Kim JR,Jang IJ,Shin SG,Yoon SH,Cho JY,Yu KS

    更新日期:2013-08-01 00:00:00

  • The pharmacological role of phosphatases (acid and alkaline phosphomonoesterases) in snake venoms related to release of purines - a multitoxin.

    abstract::Snake venom components, acting in concert in the prey, cause their immobilization and initiate digestion. To achieve this, several hydrolytic enzymes of snake venom have evolved to interfere in various physiological processes, which are well defined. However, hydrolytic enzymes such as phosphatases (acid and alkaline ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审


    authors: Dhananjaya BL,D'Souza CJ

    更新日期:2011-02-01 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


    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

  • Toxic Epidermal Necrolysis After Exposure to Dithiocarbamate Fungicide Mancozeb.

    abstract::Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disease with high mortality. Dithiocarbamates (DTC) are organosulphur compounds widely used in agriculture, industry and households. We report a case of TEN after exposure to mancozeb in fungicide. A 48-year-old 75 kg b.w. man was admitted with fever...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Zakharov S,Csomor J,Urbanek P,Pelclova D

    更新日期:2016-01-01 00:00:00

  • CYP2D6-inhibiting drugs and the increased risk of fall-related injuries due to newly initiated opioid treatment--a Swedish, register-based case-crossover study.

    abstract::It has been shown that newly initiated opioid therapy increases the risk of fall-related injuries. Yet, it remains to be determined whether drug-drug interactions can affect this negative effect, for instance with drugs inhibiting cytochrome P4502D6 (CYP2D6) that metabolizes codeine and also has a partial effect on tr...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章


    authors: Möller J,Laflamme L,Söderberg Löfdal K

    更新日期:2015-02-01 00:00:00

  • Considerations for Pharmacoepidemiological Studies of Drug-Cancer Associations.

    abstract::In this MiniReview, we provide general considerations for the planning and conduct of pharmacoepidemiological studies of associations between drug use and cancer development. We address data sources, study design, assessment of drug exposure, ascertainment of cancer outcomes, confounder adjustment and future perspecti...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审


    authors: Pottegård A,Friis S,Stürmer T,Hallas J,Bahmanyar S

    更新日期:2018-05-01 00:00:00