Identification of apoptosis signal-regulating kinase 1 (ASK1) inhibitors among the derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one

Starosyla, Sergiy A.; Volynets, Galyna P.; Lukashov, S. S.; Gorbatiuk, O. B.; Golub, Andriy G.; Bdzhola, Volodymyr G.; Yarmoluk, S. M.

doi:10.1016/j.bmc.2015.03.056

Cited by 28 publications

(8 citation statements)

References 24 publications

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“…Activated ASK1 finally promotes apoptosis via a series of cascade reactions. 64,65 Recent studies have also proven that ERS is involved in the activation of NLRP3 inflammasomes 66 After activating the unfolded protein response (UPR), ERS can promote the transcription of thioredoxin interaction protein (TXNIP) by binding IRE1α and PERK, and inhibit TXNIP by modulating miRNA-17, thereby regulating TXNIP to induce ROS production and activate NLRP3 inflammasomes. [66][67][68] Above all, we verified that the ERS/ASK1/NLRP3 inflammasome pathway is involved in the ox-LDL-induced cholesterol efflux that occurs in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

Hang

Peng

Xiang

et al. 2020

DDDT

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These authors contributed equally to this workObjective: This study was to investigate the mechanism of inflammatory pathology modification induced by ox-LDL in endothelial cells. Methodology: In this study, we firstly investigated the efflux of cholesterol of endothelial cells under the treatment of ox-LDL, and cell proliferation, ROS production, cell apoptosis was measured. Further, proteins of ASK1, NLRP3 inflammasomes and endoplasmic reticulum stress response were detected. Afterwards, ASK1 inhibitor (GS-4997) or endoplasmic reticulum stress (ERS) inhibitor (4-PBA) was used to measure the performance of endothelial cells. Results: In this study, endothelial cells were treated with ox-LDLs alone or in combination with a GS-4997 or 4-PBA. Results showed that ox-LDLs attenuated the efflux of cholesterol from endothelial cells in a dose-dependent manner. Ox-LDLs inhibited the proliferation of endothelial cells, and induced their apoptosis and production of reactive oxygen species (ROS). Additionally, ox-LDLs upregulated the levels of phosphorylated ASK1, ERS-related proteins (chop, p-PERK, GRP78, and p-IRE-1), and inflammation-associated proteins (NLRP3, IL-1β, and caspase 1) in endothelial cells. Moreover, we proved that GS-4997 could partly reverse ox-LDL-mediated cell proliferation, apoptosis, ROS production, and inflammation in endothelial cells, and increase cholesterol efflux. We also found that 4-PBA could attenuate the effects of ox-LDLs on endothelial cell cholesterol efflux, proliferation, apoptosis, ROS production, and inflammation. Conclusion: Our results suggest that cholesterol efflux from endothelial cells is reduced by ox-LDLs, and these reductions in cholesterol efflux are accompanied by increased NLRP3 inflammasome signaling, ASK1 and higher levels of endoplasmic reticulum stress. Our results suggest this axis as potential targets for treating atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

Hang

Peng

Xiang

et al. 2020

DDDT

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“…ASK1 mediates the cytotoxicity of cigarette smoke in airway epithelial cells, which is inhibited by the closely associated antioxidant thioredoxin (Lee et al, 2008). ASK1 is a good potential target for COPD, and several small molecule inhibitors have been identified (Starosyla et al, 2015). Interestingly, ASK1 knockout mice are viable, whereas p38a and JNK knockout mice are embryonically lethal.…”

Section: E Apoptosis Signal-regulating Kinase-1 Inhibitionmentioning

confidence: 99%

Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease

Barnes

2016

Pharmacol Rev

101

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“…Furan‐2‐ones are the five‐membered heterocyclic compounds possessing lactone ring in their structures and are reported to exhibit antimicrobial,, antifungal,, anti‐inflammatory, and anticancer, activities. Pyrrol‐2‐ones, on the other hand, represent an important class of five‐membered aza‐heterocycles and are well known for their wide range of pharmacological importance including DNA polymerase inhibition, signal‐regulating kinase1 (ASK1) inhibition, DRAK2 inhibition, caspase‐3 inhibition, and outstanding biological features such as anticancer, antibiotic, anti‐HIV, potential cytotoxic agents, antibiofilm agents etc . Some examples of biologically dynamic molecules possessing furan‐2‐one and pyrrol‐2‐one ring as their core center are shown in Figure .…”

Section: Introductionmentioning

confidence: 99%

Efficient and Eco‐Friendly One‐Pot Synthesis of Functionalized Furan‐2‐one, Pyrrol‐2‐one, and Tetrahydropyridine Using Lemon Juice as a Biodegradable Catalyst

Khan

Saigal

et al. 2018

ChemistrySelect

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New and facile one‐pot approach for the syntheses of polysubstituted pyrrol‐2‐one, furan‐2‐one and tetrahydropyridines (THPDs) from easily available starting materials using lemon juice as a green catalyst is presented. The synthesis of diverse furan‐2‐one and pyrrol‐2‐one derivatives were achieved from dialkyl acetylenedicarboxylates, different amines and aldehydes in high yields and short reaction times by employing 0.25 mL of lemon juice at 110 oC under solvent‐free condition. THPDs, on the other hand, were synthesized via the reaction among β‐ketoesters, various aromatic aldehydes, and amines in the presence of 0.25 mL of lemon juice in ethanol at room temperature. The molecular structure of compound pyrrol‐2‐one 7e and THPD 10g were confirmed by the single crystal X‐ray analysis. Application of cheap and green catalyst, environmentally benign reaction condition, good to high yields, applicable to a broad range of substrates and no column chromatographic separation are some salient features of this protocol.

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Identification of apoptosis signal-regulating kinase 1 (ASK1) inhibitors among the derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one

Cited by 28 publications

References 24 publications

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

<p>Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress</p>

Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease

Efficient and Eco‐Friendly One‐Pot Synthesis of Functionalized Furan‐2‐one, Pyrrol‐2‐one, and Tetrahydropyridine Using Lemon Juice as a Biodegradable Catalyst

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