O2-(6-Oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolates: a new class of nitric oxide donors activatable by GSH/GSTπ with both anti-proliferative and anti-metastatic activities against melanoma

2017 ◽  
Vol 53 (36) ◽  
pp. 5059-5062 ◽  
Author(s):  
Chengfeng Bai ◽  
Rongfang Xue ◽  
Jianbing Wu ◽  
Tian Lv ◽  
Xiaojun Luo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Donors ◽  
New Class

3c, a new nitric oxide donor activatable by GSH/GSTπ, exhibits both anti-proliferative and anti-metastatic activities against melanoma.

scholarly journals Exogenous NO Therapy for the Treatment and Prevention of Atherosclerosis

2020 ◽  
Vol 21 (8) ◽  
pp. 2703 ◽  
Author(s):  
Tommaso Gori
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Plaque Rupture ◽  
Nitric Oxide Donors ◽  
New Class ◽  
Amyl Nitrite ◽  
Treatment And Prevention ◽  
The Subject ◽  
Prevention Of Atherosclerosis ◽  
Nitric Oxide Pathway

Amyl nitrite was introduced in 1867 as the first molecule of a new class of agents for the treatment of angina pectoris. In the following 150 years, the nitric oxide pathway has been the subject of a number of pharmacological approaches, particularly since when this elusive mediator was identified as one of the most important modulators of vascular homeostasis beyond vasomotion, including platelet function, inflammation, and atherogenesis. While having potent antianginal and antiischemic properties, however, nitric oxide donors are also not devoid of side effects, including the induction of tolerance, and, as shown in the last decade, of oxidative stress and endothelial dysfunction. In turn, endothelial dysfunction is itself felt to be involved in all stages of atherogenesis, from the development of fatty streaks to plaque rupture and thrombosis. In the present review, we summarize the agents that act on the nitric oxide pathway, with a particular focus on their potentially beneficial antiatherosclerotic and unwanted pro-atherosclerotic effects.

Role of K+Channels in Augmented Relaxations to Sodium Nitroprusside Induced by Mexiletine in Rat Aortas

2000 ◽  
Vol 92 (3) ◽  
pp. 813-820 ◽  
Author(s):  
Hiroyuki Kinoshita ◽  
Toshizo Ishikawa ◽  
Yoshio Hatano
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Guanylate Cyclase ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Donors ◽  
K Channels ◽  
Vasodilator Effect ◽  
Isolated Rat

Background A class Ib antiarrhythmic drug, mexiletine, augments relaxations produced by adenosine triphosphate (ATP) sensitive K+ channel openers in isolated rat aortas, suggesting that it produces changes in the vasodilation mediated by ATP-sensitive K+ channels. Nitric oxide can induce its vasodilator effect via K+ channels, including ATP-sensitive K+ channels, in smooth muscle cells. Effects of mexiletine on arterial relaxations to nitric oxide donors, have not been studied. Therefore, the current study in isolated rat aortas was designed to (1) evaluate whether mexiletine augments relaxation in response to nitric oxide donors, including sodium nitroprusside, and (2) determine the role of K+ channels in mediating effects of mexiletine on such nitric oxide-mediated relaxation. Methods Rings of rat aortas without endothelia were suspended for isometric force recording. Concentration-response curves of sodium nitroprusside (10(-10) to 10(-5) M) and 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-9) to 10(-5) M) were obtained in the absence and in the presence of mexiletine, in combination with a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one (ODQ), or inhibitors for ATP-sensitive K+ channels (glibenclamide), inward rectifier K+ channels (BaCl2), delayed rectifier K+ channels (4-aminopyridine), large conductance Ca2+-dependent K+ channels (iberiotoxin), or small conductance Ca2+-dependent K+ channels (apamin). Results Mexiletine (10(-5) or 3 x 10(-5) M) augmented relaxations to sodium nitroprusside and NOC-7. In arteries treated with glibenclamide (10(-5) M), mexiletine (3 x 10(-5) M) did not affect relaxations to nitric oxide donors, whereas mexiletine augmented relaxations to sodium nitroprusside despite the presence of BaCl2 (10(-5) M), 4-aminopyridine (10(-3) M), iberiotoxin (5 x 10(-8) M) and apamin (5 x 10(-8) M). Relaxations to sodium nitroprusside were abolished by ODQ (5 x 10(-6) M), whereas these relaxations were augmented by mexiletine (3 x 10(-5) M) in arteries treated with ODQ (5 x 10(-6) M). Conclusions These results suggest that ATP-sensitive K+ channels in vascular smooth muscle, contribute to the augmented vasodilator effect of a nitric oxide donor, sodium nitroprusside induced by mexiletine, and that the vasodilator effect is produced, at least in part, via the guanylate cyclase-independent mechanism.

A new class of nitric oxide donors

2016 ◽  
Vol 86 (3) ◽  
pp. 158-163 ◽  
Author(s):  
S. M. Aldoshin ◽  
N. A. Sanina ◽  
M. I. Davydov ◽  
E. I. Chazov
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Donors ◽  
New Class

Enhanced gastroprotective and anti-ulcerogenic activities in rats of a new class of proton pump inhibitor containing nitrosothiol nitric oxide donor

2001 ◽  
Vol 120 (5) ◽  
pp. A144-A145 ◽  
Author(s):  
Joy K. Saha ◽  
Tiansheng Wang ◽  
Richardson Stewart ◽  
Mark Trocha ◽  
Mathew Shumway ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Proton Pump Inhibitor ◽  
Proton Pump ◽  
Nitric Oxide Donor ◽  
New Class

scholarly journals T40. GLYCERYL TRINITRATE IN FIRST EPISODE PSYCHOSIS UNMEDICATED WITH ANTIPSYCHOTICS: A RANDOMISED CONTROLLED FEASIBILITY STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S246-S247
Author(s):  
Kate Merritt ◽  
Ana Catalan ◽  
Samuel Cowley ◽  
Arsime Demjaha ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clinical Trials ◽  
Controlled Trial ◽  
Verbal Learning ◽  
Nitric Oxide Donor ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Nitric Oxide Donors ◽  
Double Blind ◽  
Randomised Controlled

Abstract Background There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent early phase studies of SNP in patients with psychosis have had mixed results, and the drug has to be administered intravenously. GTN is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. We explored the safety and effectiveness of GTN in unmedicated patients with a first episode of psychosis. Methods A single-centre, randomized, double-blind, placebo-controlled trial was conducted from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients with a first episode of psychosis were recruited from the South London and Maudsley NHS Trust, London, UK. Nineteen patients were randomised to receive 3 x sprays of GTN or placebo for 3 consecutive days, and re-assessed on Day 7. Thirteen participants were included in the final analyses. At each assessment point, symptom levels were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive performance was evaluated using the Jumping to Conclusions (JTC) and the Hopkins Verbal Learning (HVLT) tasks. Results Compared to placebo, GTN was well tolerated, but it was not associated with significant effects on either psychotic symptoms or cognition. Bayesian statistics indicated with moderate confidence that GTN does not have a therapeutic effect. Discussion This study indicates that nitric oxide donors are not therapeutically beneficial in psychosis. It also highlights the difficulties in recruiting unmedicated patients with psychosis. Future clinical trials would benefit from frameworks built into clinical services, to signpost patients not responding to medication and those discontinuing medication to clinical trials of alternatives.

scholarly journals The Application of Nitric Oxide for Ocular Hypertension Treatment

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7306
Author(s):  
Binze Han ◽  
Maomao Song ◽  
Liping Li ◽  
Xinghuai Sun ◽  
Yuan Lei
Keyword(s):  
Nitric Oxide ◽  
Ocular Hypertension ◽  
Nitric Oxide Donors ◽  
Hypertension Treatment ◽  
Aqueous Humor Outflow ◽  
New Class ◽  
Pubmed Database ◽  
Main Pathway ◽  
Outflow Pathway ◽  
Outflow System

Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure (IOP) lowering is the most effective way to slow disease progression and prevent blindness. Among the ocular hypotensive drugs currently in use, only a couple act on the conventional outflow system, which is the main pathway for aqueous humor outflow and the major lesion site resulting in ocular hypertension. Nitric oxide (NO) is a commendable new class of glaucoma drugs that acts on the conventional outflow pathway. An increasing number of nitric oxide donors have been developed for glaucoma and ocular hypertension treatment. Here, we will review how NO lowers IOP and the types of nitric oxide donors that have been developed. And a brief analysis of the advantages and challenges associated with the application will be made. The literature used in this review is based on Pubmed database search using ‘nitric oxide’ and ‘glaucoma’ as key words.

scholarly journals NCX-4040, a Unique Nitric Oxide Donor, Induces Reversal of Drug-Resistance in Both ABCB1- and ABCG2-Expressing Multidrug Human Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1680
Author(s):  
Birandra K. Sinha ◽  
Lalith Perera ◽  
Ronald C. Cannon
Keyword(s):  
Nitric Oxide ◽  
Drug Resistance ◽  
Molecular Docking ◽  
Anticancer Drugs ◽  
Abc Transporters ◽  
Human Cancer ◽  
Docking Studies ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Donors ◽  
Molecular Docking Studies

The emergence of multidrug resistance (MDR) in the clinic is a significant problem for a successful treatment of human cancers. Overexpression of various ABC transporters (P-gp, BCRP and MRP’s), which remove anticancer drugs in an ATP-dependent manner, is linked to the emergence of MDR. Attempts to modulate MDR have not been very successful in the clinic. Furthermore, no single agent has been found to significantly inhibit their functions to overcome clinical drug resistance. We have previously shown that nitric oxide (●NO) inhibits ATPase functions of ABC transporters, causing reversal of resistance to clinically active anticancer drugs. In this study, we have used cytotoxicity and molecular docking studies to show that NCX4040, a nitric oxide donor related to aspirin, inhibited the functions of ATPase which resulted in significant reversal of resistance to both adriamycin and topotecan in P-gp- and BCRP-expressing human cancer cell lines, respectively. We also used several other cytotoxic nitric oxide donors, e.g., molsidomine and S-nitroso glutathione; however, both P-gp- and BCRP-expressing cells were found to be highly resistant to these NO-donors. Molecular docking studies showed that NCX4040 binds to the nucleotide binding domains of the ATPase and interferes with further binding of ATP, resulting in decreased activities of these transporters. Our results are extremely promising and suggest that nitric oxide and other reactive species delivered to drug resistant tumor cells by well-designed nitric oxide donors could be useful in sensitizing anticancer drugs in multidrug resistant tumors expressing various ABC transporters.

scholarly journals Correction: O2-(6-Oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolates: a new class of nitric oxide donors activatable by GSH/GSTπ with both anti-proliferative and anti-metastatic activities against melanoma

2020 ◽  
Vol 56 (29) ◽  
pp. 4130-4131
Author(s):  
Chengfeng Bai ◽  
Rongfang Xue ◽  
Jianbing Wu ◽  
Tian Lv ◽  
Xiaojun Luo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Donors ◽  
New Class

Correction for ‘O2-(6-Oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolates: a new class of nitric oxide donors activatable by GSH/GSTπ with both anti-proliferative and anti-metastatic activities against melanoma’ by Chengfeng Bai et al., Chem. Commun., 2017, 53, 5059–5062.

Modulation of intrinsic cardiac neuronal activity by nitric oxide donors induces cardiodynamic changes

1995 ◽  
Vol 268 (2) ◽  
pp. R403-R413 ◽  
Author(s):  
J. A. Armour ◽  
F. M. Smith ◽  
A. M. Losier ◽  
H. H. Ellenberger ◽  
D. A. Hopkins
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Receptor Activation ◽  
Nitric Oxide Donor ◽  
Nitric Oxide Donors ◽  
Specific Marker ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Cardiac Regulation

Studies were performed to determine 1) whether a specific marker for nitric oxide production is associated with canine intrinsic cardiac neurons, 2) whether the transmembrane properties of these neurons can be altered by nitric oxide donors, 3) whether in situ intrinsic cardiac neurons are sensitive to nitric oxide donors, and 4) whether these neurons are involved in cardiac regulation. Thirty to forty percent of canine intrinsic cardiac neurons were labeled with a selective anatomic marker for nitric oxide production. Nitric oxide donors modified the transmembrane properties of a subpopulation of intrinsic cardiac neurons studied in vitro. The nitric oxide donors nitroglycerine, sodium nitrite, and nitroprusside induced concentration-dependent increases in neuronal activity frequently associated with cardiac augmentation. Similar neuronal responses were elicited by N-methyl-D-aspartate receptor activation as well as when the precursor of nitric oxide, L-arginine, and the exogenous nitric oxide donor, S-nitroso-N-acetylpenicillamine, were administered, indicating that intrinsic cardiac neurons can be modulated by nitric oxide donors. Such neurons apparently are tonically influenced by locally released nitric oxide as local administration of the competitive inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester, suppressed their spontaneous activity. These data indicate that a significant population of nitric oxide-sensitive neurons exists in the canine intrinsic cardiac nervous system that are involved in cardiac regulation.

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