Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles

Scholz, Michael; Ulbrich, Holger; Dannhardt, Gerd

doi:10.1016/j.ejmech.2007.09.007

Cited by 36 publications

(21 citation statements)

References 24 publications

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“…From these compounds, the 4‐cyclopropylbutanoyl derivative has exhibited inhibitory activity against COX and 5‐LOX, along with potent anti‐inflammatory and analgesic actions and no ulcerogenic activity in murine models . Organoselenic compounds have also been synthesized to associate dual COX/5‐LOX inhibition with antioxidant properties, namely, 1,3‐benzoselenazolin‐2‐ones, the corresponding diselenides and 4,5‐diarylisoselenazoles . Some of these compounds have indeed inhibited both COX and 5‐LOX, exerted anti‐inflammatory effects in rodent models, and displayed antioxidant activity in vitro …”

Section: Identification Of Novel Targets In the Arachidonic Acid Cascadementioning

confidence: 99%

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Pereira-Leite

Nunes

Jamal

et al. 2016

Medicinal Research Reviews

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The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) against inflammation, pain, and fever has been supporting their worldwide use in the treatment of painful conditions and chronic inflammatory diseases until today. However, the long-term therapy with NSAIDs was soon associated with high incidences of adverse events in the gastrointestinal tract. Therefore, the search for novel drugs with improved safety has begun with COX-2 selective inhibitors (coxibs) being straightaway developed and commercialized. Nevertheless, the excitement has fast turned to disappointment when diverse coxibs were withdrawn from the market due to cardiovascular toxicity. Such events have once again triggered the emergence of different strategies to overcome NSAIDs toxicity. Here, an integrative review is provided to address the breakthroughs of two main approaches: (i) the association of NSAIDs with protective mediators and (ii) the design of novel compounds to target downstream and/or multiple enzymes of the arachidonic acid cascade. To date, just one phosphatidylcholine-associated NSAID has already been approved for commercialization. Nevertheless, the preclinical and clinical data obtained so far indicate that both strategies may improve the safety of nonsteroidal anti-inflammatory therapy.

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Section: Identification Of Novel Targets In the Arachidonic Acid Cascadementioning

confidence: 99%

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Pereira-Leite

Nunes

Jamal

et al. 2016

Medicinal Research Reviews

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“…While extensively studied for pro- and anti-inflammatory effects in other conditions such as diabetes, cancer, asthma, cardiovascular disorders and most recently AD (Marks et al, 2000; Werz, 2002; Yao et al, 2005; Gubitosi-Klug et al, 2008; Ikonomovic et al, 2008; Planaguma et al, 2008; Liu et al, 2009; Menna et al, 2010; Neilson et al, 2012), LOX enzymes have not been widely explored in the context of PD etiology and progression (Mosca et al, 1996; Li et al, 1997; Mytilineou et al, 1999, 2002; Klegeris and McGeer, 2002; Canals et al, 2003; de Bernardo et al, 2004; Kramer et al, 2004; Scholz et al, 2008; Gupta et al, 2010; Dobrian et al, 2011). Further, although products of distinct LOX-mediated metabolism have differential effects on activation pro- and anti-inflammatory cellular pathways, no study has compared isozyme-specific effects on nigrostriatal dopamine regulation and vulnerability.…”

Section: Discussionmentioning

confidence: 99%

Differential contribution of lipoxygenase isozymes to nigrostriatal vulnerability

2013

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The 5- and 12/15- lipoxygenase (LOX) isozymes have been implicated to contribute to disease development in CNS disorders such as Alzheimer's disease. These LOX isozymes are distinct in function, with differential effects on neuroinflammation, and the impact of the distinct isozymes in the pathogenesis of Parkinson's disease (PD) has not as yet been evaluated. To determine whether the isozymes contribute differently to nigrostriatal vulnerability, the effects of 5- and 12/15-LOX deficiency on dopaminergic tone under na ve and toxicant-challenged conditions were tested. In na ve mice deficient in 5-LOX expression, a modest but significant reduction (18.0% reduction vs. wildtype (WT)) in striatal dopamine (DA) was detected (n=6-8 per genotype). A concomitant decline in striatal tyrosine hydroxylase (TH) enzyme was also revealed in null 5-LOX vs. WT mice (26.2%); however, no changes in levels of DA or TH immunoreactivity were observed in null 12/15-LOX vs. WT mice. When challenged with the selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), WT mice showed marked reduction in DA (31.9%) and robust astrocytic and microglial activation as compared to saline-treated animals. In contrast, null 5-LOX littermates demonstrated no significant striatal DA depletion or astrogliosis (as noted by Western blot analyses for GFAP immunoreactivity). In na ve null 12/15-LOX mice, no significant change in striatal DA values was observed compared to WT, and following MPTP treatment, the transgenics revealed striatal DA reduction similar to the challenged WT mice. Taken together, these data provide the first evidence that: (i) LOX isozymes are involved in the maintenance of normal dopaminergic function in the striatum, and (ii) the 5- and 12/15-LOX isozymes contribute differentially to striatal vulnerability in response to neurotoxicant challenge.

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“…After cooling to rt, the mixture was poured into a solution of saturated aqueous sodium hydrogen carbonate (100 ml) and extracted three times with ether. The combined organic layers were dried over anhydrous Na 2 SO 4 Compound 3 was prepared in a manner analogous to reference [6]. A mixture of 2 (10 mmol) and ethyl 2-bromoacetate (30 mmol) in 50 ml dry ethanol was heated under reflux for 6 h. The preparation was concentrated under reduced pressure.…”

Section: 5-di(4-methoxyphenyl)-isothiazolementioning

confidence: 99%

Investigations Concerning the Correlation of COX‐1 Inhibitory and Hydroxyl Radical Scavenging Activity

Scholz

Ulbrich

Mattern

et al. 2008

Archiv der Pharmazie

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The aim was to study the COX-1 inhibiting efficacy in context with hydroxyl radical scavenging properties of compounds bearing a carboxylic acid and ester function, respectively. In general, the acids are more potent radical scavengers than the corresponding esters but there is no clear correlation with their COX-1 inhibiting potencies. A feasible scavenging mechanism of carboxylic acids is discussed.

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Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles

Cited by 36 publications

References 24 publications

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Differential contribution of lipoxygenase isozymes to nigrostriatal vulnerability

Investigations Concerning the Correlation of COX‐1 Inhibitory and Hydroxyl Radical Scavenging Activity

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