N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase

Maccallini, Cristina; Patruno, Antonia; Lannutti, F; Ammazzalorso, Alessandra; Filippis, Barbara De; Fantacuzzi, Marialuigia; Franceschelli, Sara; Giampietro, Letizia; Masella, Simona; Felaco, Mario; Re, Nazzareno; Amoroso, Rosa

doi:10.1016/j.bmcl.2010.09.059

Cited by 25 publications

(14 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacokinetic studies showed that 1400W is an irreversible or an extremely slowly reversible inhibitor of NOS2, although it has been reported to be active for a few hours after administration [ 32 , 33 ]. In the continuous effort to develop even more selective and effective NOS2 inhibitors, different acetamidines structurally related to the 1400W leading scaffold have been published [ 31 , 34 , 35 , 36 , 37 ], thus confirming the growing interest in the pharmacologic potential of NOS2 activity inhibition in different diseases, including GBM.…”

Section: Introductionmentioning

confidence: 98%

Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation

Palumbo

Lombardi

Siragusa

et al. 2018

IJMS

View full text Add to dashboard Cite

Aberrant nitric oxide synthase 2 (NOS2) expression has been suggested as an interesting therapeutic target that is being implicated as a component of the molecular profile of several human malignant tumors, including glioblastoma, which is the most aggressive brain tumor with limited therapeutic options and poor prognosis. The aim of the present work was to evaluate the effect of 1400W, a specific NOS2 inhibitor, on human glioma cells in terms of clonogenic potential, proliferation, migration rate, and neurosphere generation ability. NOS2 expression was determined by Western blotting. Nitric oxide (NO) production was measured through nitrite level determination. The trypan blue exclusion test and the plate colony formation assay were performed to evaluate cell proliferation and clonogenic potential. Cell proliferation and migration ability was assessed by the in vitro wound-healing assay. Neurosphere generation in a specific stemcell medium was investigated. NOS2 was confirmed to be expressed in both the glioma cell line and a human glioma primary culture, and overexpressed in relative derived neurospheres. Experiments that aimed to evaluate the influence of 1400W on U-87 MG, T98G (glioblastoma cell lines) and primary glioma cells sustained the crucial role played by NOS2 in proliferation, colony formation, migration, and neurosphere generation, thus supporting the emerging relevance of a NOS2/NO system as a prognostic factor for glioma malignancy and recurrence.

show abstract

Section: Introductionmentioning

confidence: 98%

Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation

Palumbo

Lombardi

Siragusa

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…In the condition of oxidative stress, nitric oxide was produced through the activation of inducible isoform iNOS with formation to elevate concentration of nitric oxide and thus of peroxynitrite (ONOO − ). As nitric oxide is a main signalling molecule in cells, its overproduction may lead to pathological effects in several organ systems . Wide quantities of nitric oxide were found in human gastro‐junction, and it can diffuse epithelial mucosa and contribute to the increase in the GERD pathological condition.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: A new biological vision

Franceschelli

Gatta

Pesce

et al. 2018

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Gastroesophageal reflux disease (GERD), a clinical condition characterized by reflux of gastroduodenal contents in the oesophagus, has proved to demonstrate a strong link between oxidative stress and the development of GERD. Proton pump inhibitors (PPIs) have been universally accepted as first‐line therapy for management of GERD. The potential benefits of electrolysed reduced water (ERW), rich in molecular hydrogen, in improving symptoms and systemic oxidative stress associated with GERD was assessed. The study was performed on 84 GERD patients undergoing control treatment (PPI + tap water) or experimental treatment (PPI + ERW) for 3 months. These patients were subjected to the GERD‐Health Related Quality of Life Questionnaire as well as derivatives reactive oxigen metabolites (d‐ROMs) test, biological antioxidant potential (BAP) test, superoxide anion, nitric oxide and malondialdehyde assays, which were all performed as a proxy for the oxidative/nitrosative stress and the antioxidant potential status. Spearman's correlation coefficient was used to evaluate the correlation between scores and laboratory parameters. Overall results demonstrated that an optimal oxidative balance can be restored and GERD symptoms can be reduced rapidly via the integration of ERW in GERD patients. The relative variation of heartburn and regurgitation score was significantly correlated with laboratory parameters. Thus, in the selected patients, combination treatment with PPI and ERW improves the cellular redox state leading to the improvement of the quality of life as demonstrated by the correlation analysis between laboratory parameters and GERD symptoms.

show abstract

“…All chemicals reagents and solvents were of analytical grade and were used as received. The 1-benzyl-2-methylimidazole (bmim) was synthesised following a literature procedure 14 starting from 2-methylimidazole and benzyl chloride (see Supplementary Material ). 1 H-NMR and 13 C-NMR spectra were recorded on Bruker Avance DPX250 spectrometers (Constantine, Algeria).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, X-ray structure, in silico calculation, and carbonic anhydrase inhibitory properties of benzylimidazole metal complexes

Bouchouit

Bouacida

Zouchoune

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Three coordination compounds of formula {M(bmim)2Cl2} were synthetised (M = Co, Zn, and Hg) and fully characterised. Each complex incorporates 1-benzyl-2-methylimidazole (bmim) as ligand. The coordination polyhedron around the metal center for all complexes has a quasi-regular tetragonal geometry. Density functional theory calculations were carried out on the title compounds and as well on hypothetical complexes (Cu, Ni), in order to elucidate their electronic and molecular structure. The calculations reproduced the Co, Zn, and Hg experimental structures and could predict stable complexes in the case of Ni(II) and Cu(II) ions. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the three complexes were investigated. Only compound {Hg(bmim)2Cl2} (3) exhibited a modest inhibitory effect against hCA I, probably due to the affinity of Hg(II) for His residues at the entrance of the active site cavity.

show abstract

N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase

Cited by 25 publications

References 30 publications

Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation

Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation

Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen: A new biological vision

Synthesis, X-ray structure, in silico calculation, and carbonic anhydrase inhibitory properties of benzylimidazole metal complexes

Contact Info

Product

Resources

About