Novel 2-Phenylimidazo[1,2-a]pyridine Derivatives as Potent and Selective Ligands for Peripheral Benzodiazepine Receptors:  Synthesis, Binding Affinity, and in Vivo Studies

1999 ◽  
Vol 42 (19) ◽  
pp. 3934-3941 ◽  
Author(s):  
Giuseppe Trapani ◽  
Massimo Franco ◽  
Andrea Latrofa ◽  
Angelo Carotti ◽  
Mariangela Serra ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Benzodiazepine Receptors ◽  
In Vivo Studies ◽  
Pyridine Derivatives ◽  
Peripheral Benzodiazepine Receptors ◽  
Selective Ligands

In vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors

Glia ◽  
2007 ◽  
Vol 55 (14) ◽  
pp. 1459-1468 ◽  
Author(s):  
Hervé Boutin ◽  
Fabien Chauveau ◽  
Cyrille Thominiaux ◽  
Bertrand Kuhnast ◽  
Marie-Claude Grégoire ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Benzodiazepine Receptors ◽  
Brain Lesions ◽  
Peripheral Benzodiazepine Receptors

scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

scholarly journals A Bifunctional Adsorber Particle for the Removal of Hydrophobic Uremic Toxins from Whole Blood of Renal Failure Patients

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 389 ◽  
Author(s):  
Marieke Sternkopf ◽  
Sven Thoröe-Boveleth ◽  
Tobias Beck ◽  
Kirsten Oleschko ◽  
Ansgar Erlenkötter ◽  
...  
Keyword(s):  
Adsorption Capacity ◽  
Binding Affinity ◽  
Whole Blood ◽  
Uremic Toxins ◽  
In Vivo Studies ◽  
Uremic Toxin ◽  
High Binding ◽  
High Binding Affinity

Hydrophobic uremic toxins accumulate in patients with chronic kidney disease, contributing to a highly increased cardiovascular risk. The clearance of these uremic toxins using current hemodialysis techniques is limited due to their hydrophobicity and their high binding affinity to plasma proteins. Adsorber techniques may be an appropriate alternative to increase hydrophobic uremic toxin removal. We developed an extracorporeal, whole-blood bifunctional adsorber particle consisting of a porous, activated charcoal core with a hydrophilic polyvinylpyrrolidone surface coating. The adsorption capacity was quantified using analytical chromatography after perfusion of the particles with an albumin solution or blood, each containing mixtures of hydrophobic uremic toxins. A time-dependent increase in hydrophobic uremic toxin adsorption was depicted and all toxins showed a high binding affinity to the adsorber particles. Further, the particle showed a sufficient hemocompatibility without significant effects on complement component 5a, thrombin-antithrombin III complex, or thrombocyte concentration in blood in vitro, although leukocyte counts were slightly reduced. In conclusion, the bifunctional adsorber particle with cross-linked polyvinylpyrrolidone coating showed a high adsorption capacity without adverse effects on hemocompatibility in vitro. Thus, it may be an interesting candidate for further in vivo studies with the aim to increase the efficiency of conventional dialysis techniques.

Synthesis of substituted [123I]imidazo[1,2-α]pyridines as potential probes for the study of the peripheral benzodiazepine receptors using SPECT

2000 ◽  
Vol 88 (3-4) ◽  
Author(s):  
Andrew Katsifis ◽  
F. Mattner ◽  
B. Dikic ◽  
V. Papazian
Keyword(s):  
Benzodiazepine Receptors ◽  
High Affinity ◽  
Peripheral Benzodiazepine Receptors ◽  
Selective Ligands

The imidazo[1,2-α]pyridines [N,N´-dimethyl-6-chloro-(4´zf-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 1, [N,N´l-6-chloro-(4´-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 2, and [N-methyl-6-chloro-(4´-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 3, are high affinity and selective ligands for the Peripheral Benzodiazepine Receptors (PBR). The [

Coumarins and Quinolones as Effective Multiple Targeted Agents Versus Covid-19: An in Silico Study

2021 ◽  
Vol 17 ◽  
Author(s):  
Mojgan Nejabat ◽  
Razieh Ghodsi ◽  
Farzin Hadizadeh
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Oral Absorption ◽  
Antiviral Agent ◽  
In Vivo Studies ◽  
Reference Drug ◽  
Viral Proteases ◽  
In Silico Study

Background: The Covid-19 virus emerged a few months ago in China and infections rapidly escalated into a pandemic. Objective: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential. Method: In this work two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds. Result: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets – S2, TMPRSS2 and furin – simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza. Conclusion: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.

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