Recent developments in nitric oxide donor drugs

Miller, Mark R.; Megson, Ian L.

doi:10.1038/sj.bjp.0707224

Cited by 552 publications

(449 citation statements)

References 220 publications

Supporting

Mentioning

432

Contrasting

Unclassified

Order By: Relevance

“…Cells were treated with the following drugs: 10 μM 1H- [1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, an inhibitor of soluble guanylate cyclase; Cayman Chemical) or 50 μM 1-methyl-3-isobutylxanthine (IBMX, a non-specific phosphodiesterase inhibitor; Cayman Chemical) for 1 h; 1 μM vardenafil (a phosphodiesterase V inhibitor; Toronto Research Chemicals, Toronto, Canada), 1 μM Rp-8-pCPT-cGMPS (a PKG inhibitor; BioLog, Farmingdale, NY), 25 μM 8-pCPT-cGMPS (a membrane-permeable form of cGMP that activates PKG; BioLog), or 5 μM 8-CPT-cAMP (an activator of both cAMP-dependent protein kinase (PKA) and PKG, and of EPAC; BioLog) added at 0, 4, 9 and 24 h; or 10 μM PP2 or PP3 (a Srcspecific inhibitor and its non-functional analog, respectively; Cayman Chemical) or 5 μM U1026 (a MEK-specific inhibitor, Promega; Madison, WI) for 30 h.…”

Section: Pharmacological Treatmentsmentioning

confidence: 99%

See 1 more Smart Citation

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Spitler

Schwappacher

et al. 2013

Cellular Signalling

View full text Add to dashboard Cite

a b s t r a c t a r t i c l e i n f oNitric oxide (NO) donors have been shown to improve wound healing, but the mechanism is not well defined. Here we show that the novel NO donor nitrosyl-cobinamide (NO-Cbi) improved in vitro wound healing in several cell types, including an established line of lung epithelial cells and primary human lung fibroblasts. On a molar basis, NO-Cbi was more effective than two other NO donors, with the effective NO-Cbi concentration ranging from 3 to 10 μM, depending on the cell type. Improved wound healing was secondary to increased cell migration and not cell proliferation. The wound healing effect of NO-Cbi was mediated by cGMP, mainly through cGMPdependent protein kinase type I (PKGI), as determined using pharmacological inhibitors and activators, and siRNAs targeting PKG type I and II. Moreover, we found that Src and ERK were two downstream mediators of NO-Cbi's effect. We conclude that NO-Cbi is a potent inducer of cell migration and wound closure, acting via cGMP, PKG, Src, and extracellular signal regulated kinase (ERK).

show abstract

Section: Pharmacological Treatmentsmentioning

confidence: 99%

“…Nitric oxide (NO) and NO donors such as sydnonimines, diazeniumdiolates, S-nitrosothiols, and NO-containing nanoparticles have been shown to improve wound healing to varying degrees [1,2]. These agents have been studied in vitro, in airway and gastric epithelial wounds [3,4], and in vivo, in diabetic ulcers [5], and skin abscesses [6].…”

Section: Introductionmentioning

confidence: 99%

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Spitler

Schwappacher

et al. 2013

Cellular Signalling

View full text Add to dashboard Cite

show abstract

“…In the cardiovascular system NO predominates in large conduits, which supports its primarily anti-atherothrombotic effects (Miller et al, 2008(Miller et al, , 2000Miller and Megson, 2007;Schade et al, 2010). NO contributes to control the vascular endothelium smooth muscle cells tone and platelets' adhesion and aggregation (Miller and Megson, 2007;Moncada et al, 1991;Murad, 2006;Scatena et al, 2010;Schade et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

Candia

Marini

Zaetta

et al. 2015

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

A number of new nitric oxide (NO)-precursors were synthesized by grafting nitrate-containing moieties on the structures of the benzyloxy isonipecotanilide derivatives 1 and 2 already reported as moderately potent antiplatelet agents. Various nitrooxy (ONO2)-alkyl side chains were covalently linked to the piperidine nitrogen of the parent compounds through carbamate and amide linkage, and the synthesis of a benzyl nitrate analog (15) of compound 1 was also achieved. The in vitro vasodilatory activities, as well as platelet anti-aggregatory effects, of the newly synthesized organic nitrates were assessed. The (ONO2)methyl carbamate-based derivative 5a and the benzyl nitrate analog 15, which on the other hand retain activity as inhibitors of ADP-induced platelet aggregation, exhibited strong NO-mediated vasodilatory effects on pre-contracted rat aorta strips, with EC50 values in the low nanomolar range (13 and 29 nM, respectively). Experiments carried out with the selectively inhibited soluble guanylate cyclase (sGC), which is the key enzyme of the NO-mediated pathway leading to vascular smooth muscle relaxation, confirmed the involvement of NO in the observed vasodilation. The nitrate derivatives proved to be stable in acidic aqueous solution and at pH 7.4. In human serum, unlike 5a, which showed not to undergo enzyme-catalyzed decomposition, the other tested (ONO2)-alkyl carbamate-based compounds (5b and 5e) and benzyl nitrate 15 underwent a faster degradation. However, their decomposition rates in serum were quite slow (t½ > 2.6 h), which suggests that nitrate moiety is poorly metabolized in blood plasma and that much of the in vitro antiplatelet activity has to be attributed to the intact (ONO2)-containing molecules.

show abstract

“…There are some representative chemical classes of NO-donors (Figure 1), as S-nitrosothiols (RSNOs), diazeniumdiolates (NONOates), organic nitrates and nitrites, and metal nitrosyl complexes, which were recently reviewed (Miller, Megson, 2007;Keefer, 2011;Tfouni et al, 2012;Serafim et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide releasing-dendrimers: an overview

Roveda

Franco

2013

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.

show abstract

Recent developments in nitric oxide donor drugs

Cited by 552 publications

References 220 publications

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

Nitrosyl-cobinamide (NO-Cbi), a new nitric oxide donor, improves wound healing through cGMP/cGMP-dependent protein kinase

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

Nitric oxide releasing-dendrimers: an overview

Contact Info

Product

Resources

About