α-Phenyl-N-tert-butyl nitrone (PBN) derivatives: Synthesis and protective action against microvascular damages induced by ischemia/reperfusion

Kim, Sothea; Vilela, Guilherme V.M. de A.; Bouajila, Jalloul; Dias, Ayres G.; Cyrino, Fátima Z. G. A.; Bouskela, Eliete; Costa, Paulo R.R.; Nepveu, Françoise

doi:10.1016/j.bmc.2007.02.033

Cited by 30 publications

(18 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, this chemical property of PBN is increasingly invoked to explain some of its pharmacological actions [16,18]. Among the increasing number of available PBNs designed for a therapeutic purpose, most were elaborated on the basis of cell targeting, bioavailability or increased membrane crossing [13,19,20], and if a few were built around a phenolic-based antioxidant scaffold [21][22][23][24] (Figure 1A), no further structural modification of the non aromatic side of the nitrone function was done to improve the EPR detection of spin adducts. 9 significantly decreased with increasing steric bulk of the substituent.…”

Section: Introductionmentioning

confidence: 99%

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

Cassien

Petrocchi

Thétiot-Laurent

et al. 2016

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential and NO donation properties in vitro, their cytotoxicity and on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl-and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, 4g−i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.

show abstract

Section: Introductionmentioning

confidence: 99%

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

Cassien

Petrocchi

Thétiot-Laurent

et al. 2016

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Several HPLC assays for TMP and/or related nitrones have been described (Liang et al 1999;Lees et al 2001;Edenius et al 2002;Kim et al 2007). Based on the reported studies, we optimized the chromatographic conditions for separation and detection of TBN.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic study of a novel stroke therapeutic, 2-[[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine, by a simple HPLC–UV method in rats

Chen

Wang

et al. 2011

Eur J Drug Metab Pharmacokinet

View full text Add to dashboard Cite

2-[[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine (TMP), was found to be a potent candidate compound for ischemic stroke treatment. It is currently in preclinical development as a stroke therapeutic. To study its pharmacokinetic characteristics, a simple and rapid HPLC-UV method was developed and validated to quantitatively determine TBN concentration in rat plasma. A Purospher C(18) column (150 × 4.6 mm, 5 μm) was used for analysis with a mobile phase containing methanol-potassium dihydrogen phosphate buffer solution (50 mM, pH 3.0) (45:55, v/v) and UV detection at 295 nm. The pharmacokinetic study was conducted in Sprague-Dawley rats by intravenous (i.v. 40, 80, and 160 mg/kg) and intragastric (i.g. 80 mg/kg) administration. The concentration-time profiles of TBN in plasma fitted a two-compartment model for both administration routes. The elimination half-life (T (1/2) (β)) of i.v. administration ranged from 134 to 225 min for low, middle and high dosage, and the area under the concentration-time curve from zero to infinity (AUC((0-∞))) ranged from 7,954 to 49,804 μg min/mL. Compared with the parent compound TMP, TBN showed a longer T (1/2) (β) (TBN 134.52 min, TMP 91.85 min) and a higher AUC((0-∞)) (TBN 22,687.84 μg min/mL, TMP 7,287.98 μg min/mL) after the same dosage of intravenous administration (80 mg/kg). The intragastric administration of TBN had a peak time of 21.65 min, C (max) of 41.71 μg/mL, and k (a) of 0.19 min(-1). And the absolute bioavailability was 36.02%.

show abstract

“…17, again a tert-butyl-nitrone, but with 4-pyrrolidine-1,8-naphthylimido-benzylidene as fluorescent moiety. 4-(1,3-Dioxacyclopent-2-yl)benzonitrile B was synthesized according to Ouari et al, 1998 in good yield and in the last step the formation of the nitrone 3 was carried out according to Kim et al, 2007. …”

Section: -Pyrrolidine-18-naphthylimido-methylphenyl-tert-butyl-nitrmentioning

confidence: 99%

Fluorescent Nitrones for the Study of ROS Formation with Subcellular Resolution

Hauck¹,

Lorat²,

Leinisch³

et al. 2012

Nitroxides - Theory, Experiment and Applications

View full text Add to dashboard Cite

α-Phenyl-N-tert-butyl nitrone (PBN) derivatives: Synthesis and protective action against microvascular damages induced by ischemia/reperfusion

Cited by 30 publications

References 48 publications

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

Pharmacokinetic study of a novel stroke therapeutic, 2-[[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine, by a simple HPLC–UV method in rats

Fluorescent Nitrones for the Study of ROS Formation with Subcellular Resolution

Contact Info

Product

Resources

About