Impact of novel <i>N</i>-aryl piperamide NO donors on NF-κB translocation in neuroinflammation: rational drug-designing synthesis and biological evaluation

Shahbazi, Sajad; Kaur, Jagdeep; Singh, Shikha; Achary, K. Gopinath; Wani, Sameena; Jema, Sobhagyalaxmi; Akhtar, Jabed; Sobti, Ranbir Chander

doi:10.1177/1753425917740727

Cited by 9 publications

(5 citation statements)

References 51 publications

(60 reference statements)

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“…Another relevant ω-3 fatty acid, docosahexaenoic acid (DHA), did not show any significant stimulatory effect on IL-6 production [43]. In addition, the CHME3 cells were found to release other cytokines, including IL-12 and IFNγ, in response to LPS [52].…”

Section: Functional Properties Cytokine and Chemokine Productionmentioning

confidence: 98%

The human microglial HMC3 cell line: where do we stand? A systematic literature review

Russo

Cappoli

Coletta

et al. 2018

J Neuroinflammation

163

130

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Microglia, unique myeloid cells residing in the brain parenchyma, represent the first line of immune defense within the central nervous system. In addition to their immune functions, microglial cells play an important role in other cerebral processes, including the regulation of synaptic architecture and neurogenesis. Chronic microglial activation is regarded as detrimental, and it is considered a pathogenic mechanism common to several neurological disorders. Microglial activation and function have been extensively studied in rodent experimental models, whereas the characterization of human cells has been limited due to the restricted availability of primary sources of human microglia. To overcome this problem, human immortalized microglial cell lines have been developed. The human microglial clone 3 cell line, HMC3, was established in 1995, through SV40-dependent immortalization of human embryonic microglial cells. It has been recently authenticated by the American Type Culture Collection (ATCC®) and distributed under the name of HMC3 (ATCC®CRL-3304). The HMC3 cells have been used in six research studies, two of which also indicated by ATCC® as reference articles. However, a more accurate literature revision suggests that clone 3 was initially distributed under the name of CHME3. In this regard, several studies have been published, thus contributing to a more extensive characterization of this cell line. Remarkably, the same cell line has been used in different laboratories with other denominations, i.e., CHME-5 cells and C13-NJ cells. In view of the fact that “being now authenticated by ATCC®” may imply a wider distribution of the cells, we aimed at reviewing data obtained with the human microglia cell line clone 3, making the readers aware of this complicated nomenclature. In addition, we also included original data, generated in our laboratory with the HMC3 (ATCC®CRL-3304) cells, providing information on the current state of the culture together with supplementary details on the culturing procedures to obtain and maintain viable cells.

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Section: Functional Properties Cytokine and Chemokine Productionmentioning

confidence: 98%

The human microglial HMC3 cell line: where do we stand? A systematic literature review

Russo

Cappoli

Coletta

et al. 2018

J Neuroinflammation

163

130

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“… 162 NO donors that increase tissue NO levels are being developed as novel therapies for other diseases. 163 , 164 A long-lasting albumin-based NO donor (S-nitrosated human albumin) was tested in murine models of chronic renal disease and was shown to have efficacy in reducing renal fibrosis, inflammation, oxidative stress, and TGF-β levels. 165 Thus, NO donor approaches could be tested as disease-modifying therapies for limiting the progression of COPD phenotypes in which endothelial dysfunction plays a significant role.…”

Section: Therapeutic Approaches Targeting Endothelial Dysfunction In mentioning

confidence: 99%

“…Inhaled NO therapy reduced PAPs and PVR, and increased exercise tolerance without decreasing arterial oxygenation 162 . NO donors that increase tissue NO levels are being developed as novel therapies for other diseases 163 , 164 . A long‐lasting albumin‐based NO donor (S‐nitrosated human albumin) was tested in murine models of chronic renal disease and was shown to have efficacy in reducing renal fibrosis, inflammation, oxidative stress, and TGF‐β levels 165 .…”

Section: Therapeutic Approaches Targeting Endothelial Dysfunction In Copdmentioning

confidence: 99%

COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

2018

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Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients.

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“…Figure 4 shows the possible mechanism of action of analogues on NF-kB and Nrf2, based on previous studies that mention the interaction of these aryl amides with proinflammatory cytokines. [46,[55][56][57][58][59] c = values of cLogP were calculated by DataWarrior. [33] The results are the means (� SD) of three separate experiments performed in triplicate.…”

Section: Resultsmentioning

confidence: 99%

“…In this sense, our results show that N ‐benzyl linoleamide analogues act by inhibiting NF‐κB and activating Nrf2. Figure shows the possible mechanism of action of analogues on NF‐κB and Nrf2, based on previous studies that mention the interaction of these aryl amides with proinflammatory cytokines …”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Pharmacological Evaluation ofN‐Benzyl Linoleamide Analogues fromTropaeolum tuberosumas NF‐κB Inhibitors and Nrf2 Activators

et al. 2020

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Nineteen N-benzyl linoleamide analogues (macamide from Tropaeolum tuberosum) were synthesised, modifying the molecular structure (benzyl position, aromatic ring and carbonyl group). The structures were confirmed using nuclear magnetic resonance and mass spectrometry techniques. Cell viability and anti-inflammatory activity of these compounds were evaluated in three brain cell lines (C8-D1 A, Neuro-2a, and EOC 13.31). Regarding the effect on NF-kB, several analogues had better inhibition potential than their natural precursor (N-benzyl linoleamide), being the N-(1-(3,5-dimethyl-α-methylbenzyl)-linolethiamide the most active, with IC 50 values of 0.01 � 0.01, 0.01 � 0.01 and 0.02 � 0.01 μM, respectively. Finally, all analogues activated Nrf2, with the same compound being the most active, presenting EC 50 values of 0.03 � 0.01, 0.07 � 0.01 and 0.11 � 0.02 nM, respectively. Analysing the link between chemical structure and pharmacological activity, our study shows that the changes made to N-benzyl linoleamide lead us to obtaining an analogue with greater anti-inflammatory activity than its precursor and with potential for the treatment of migraine.

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Impact of novel N-aryl piperamide NO donors on NF-κB translocation in neuroinflammation: rational drug-designing synthesis and biological evaluation

Cited by 9 publications

References 51 publications

The human microglial HMC3 cell line: where do we stand? A systematic literature review

The human microglial HMC3 cell line: where do we stand? A systematic literature review

COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

Design, Synthesis and Pharmacological Evaluation ofN‐Benzyl Linoleamide Analogues fromTropaeolum tuberosumas NF‐κB Inhibitors and Nrf2 Activators

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