Synthesis and evaluation of benzoxazinone derivatives on activity of human neutrophil elastase and on hemorrhagic shock-induced lung injury in rats

Hsieh, Pei‐Wen; Yu, Huang-Ping; Chang, Yi-Ju; Hwang, Tsong‐Long

doi:10.1016/j.ejmech.2010.03.046

Cited by 29 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibitory effects of these compounds on NE were related to the position of the chloro-substituent in the A ring. These compounds also demonstrated antiplatelet aggregation effects and protected rats from hemorrhagic shock-induced lung injury [81,83].…”

Section: Heterocyclic Inhibitorsmentioning

confidence: 97%

“…Their beneficial effects were tested in a rat LPSinduced acute lung injury model. The benzoxazinones are known as heterocyclic acylating compounds that inhibit human NE via a mechanism involving the formation of an acyl enzyme intermediate [81,82]. In a previous study, a new series of benzoxazinone analogs were identified, and these analogs exerted potent dual inhibitory effects on NE activity and superoxide anion generation in formyl-L-methionyl-Lleucyl-L-phenylalanine -activated human neutrophils.…”

Section: Heterocyclic Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Neutrophil elastase inhibitors: a patent review and potential applications for inflammatory lung diseases (2010 – 2014)

Tsai¹,

Hwang²

2015

Expert Opinion on Therapeutic Patents

Self Cite

View full text Add to dashboard Cite

According to this review of recent NE inhibitor patents, all of the disclosed inhibitors can be classified into peptide- and non-peptide-based groups. The non-peptide NE inhibitors include heterocyclics, uracil derivatives and deuterium oxide. Among the heterocyclic analogs, derivatives of pyrimidinones, tetrahydropyrrolopyrimidinediones, pyrazinones, benzoxazinones and hypersulfated disaccharides were introduced. The literature has increasingly implicated NE in the pathogenesis of various diseases, of which inflammatory destructive lung diseases remain a major concern. However, only a few agents have been validated for therapeutic use in clinical settings to date.

show abstract

Section: Heterocyclic Inhibitorsmentioning

confidence: 97%

Section: Heterocyclic Inhibitorsmentioning

confidence: 99%

Neutrophil elastase inhibitors: a patent review and potential applications for inflammatory lung diseases (2010 – 2014)

Tsai¹,

Hwang²

2015

Expert Opinion on Therapeutic Patents

Self Cite

View full text Add to dashboard Cite

show abstract

“…Meo-Suc-Ala-Ala-Pro-Val-p-nitroanide was employed as the substrate of elastase for detecting elastase release [60]. After the incorporation with the substrate (100 μM), the cells were equilibrated for 2 min and then treated with the nanoformulations for 5 min.…”

Section: Elastase Releasementioning

confidence: 99%

Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Liu

Umoro

et al. 2020

J Nanobiotechnol

Self Cite

View full text Add to dashboard Cite

Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the antiinflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

show abstract

“… Neutrophil elastase based inhibitors ; Pyrimidinone, Pyrimidinedione, and Pyrimidine derivative s are act as NE inhibitors. The IC 50 values of dihydropyrimidinone (0.3 nM), pyrimidinone (0.61 nM), tetra hydro pyrrolo pyrimidinediones (0.20 nM), 2-pyrazinone derivative (0.33 nM), 2-pyridone derivatives (3.5 nM), benzoxazinone derivatives (15 nM), uracil derivatives (3.5 nM) (Gadek and Pacht, 1990 ; Vandivier et al, 2002 ; Iba et al, 2006 ), sivelestat (46 nM), indicate that above derivatives are potential inhibitors (Ainge et al, 2010 ; Hsieh et al, 2010 ; Ray et al, 2010 ; Bergstrom et al, 2011 ; Von Nussbaum et al, 2012 ). Abbreviation used in the figures A and E both represent C—R 7 or one of the two ring members A and E represents N and the other represents C—R 7 , in which R 7 represents in each case hydrogen, fluorine or chlorine, Z represents O or S, n represents the number 0, 1, or 2.…”

Section: Inhibitor Based On Neutrophil Elastasementioning

confidence: 99%

Role of Proteases in Chronic Obstructive Pulmonary Disease

Pandey¹,

Mishra

2017

Front. Pharmacol.

113

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is generally associated with progressive destruction of airways and lung parenchyma. Various factors play an important role in the development and progression of COPD, like imbalance of proteases, environmental and genetic factors and oxidative stress. This review is specifically focused on the role of proteases and their imbalance in COPD. There are three classes (serine, mettalo, and cysteine) of proteases involved in COPD. In serine proteases, neutrophil elastase, cathepsin G, and proteinase-3 are involved in destruction of alveolar tissue. Matrix-mettaloproteinase-9, 12, 13, plays an influential role in severity of COPD. Among cysteine proteases, caspase-3, caspases-8 and caspase-9 play an important role in controlling apoptosis. These proteases activities can be regulated by inhibitors like α-1-antitrypsin, neutrophil elastase inhibitor, and leukocyte protease inhibitor. Studies suggest that neutrophil elastase may be a therapeutic target for COPD, and specific inhibitor against this enzyme has potential role to control the disease. Current study suggests that Dipeptidyl Peptidase IV is a potential marker for COPD. Since the expression of proteases and its inhibitors play an important role in COPD pathogenesis, therefore, it is worth investigating the role of proteases and their regulation. Understanding the biochemical basis of COPD pathogenesis using advanced tools in protease biochemistry and aiming toward translational research from bench-to-bedside will have great impact to deal with this health problem.

show abstract

Synthesis and evaluation of benzoxazinone derivatives on activity of human neutrophil elastase and on hemorrhagic shock-induced lung injury in rats

Cited by 29 publications

References 31 publications

Neutrophil elastase inhibitors: a patent review and potential applications for inflammatory lung diseases (2010 – 2014)

Neutrophil elastase inhibitors: a patent review and potential applications for inflammatory lung diseases (2010 – 2014)

Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Role of Proteases in Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About