scholarly journals Design, Synthesis, and Validation of a Novel [11C]Promethazine PET Probe for Imaging Abeta Using Autoradiography

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2182
Author(s):  
Clayton A. Whitmore ◽  
Mariam I. Boules ◽  
William J. Behof ◽  
Justin R. Haynes ◽  
Dmitry Koktysh ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
In Vivo Studies ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Molar Activity ◽  
Rp Hplc ◽  
Model Of Alzheimer’S Disease ◽  
Antihistamine Drug

Promethazine, an antihistamine drug used in the clinical treatment of nausea, has been demonstrated the ability to bind Abeta in a transgenic mouse model of Alzheimer’s disease. However, so far, all of the studies were performed in vitro using extracted tissues. In this work, we report the design and synthesis of a novel [11C]promethazine PET radioligand for future in vivo studies. The [11C]promethazine was isolated by RP-HPLC with radiochemical purity >95% and molar activity of 48 TBq/mmol. The specificity of the probe was demonstrated using human hippocampal tissues via autoradiography.

scholarly journals A novel antioxidant ergothioneine PET radioligand for in vivo imaging applications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
William J. Behof ◽  
Clayton A. Whitmore ◽  
Justin R. Haynes ◽  
Adam J. Rosenberg ◽  
Mohammed N. Tantawy ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mouse Model ◽  
Peripheral Tissues ◽  
Molar Activity ◽  
Model Of Alzheimer’S Disease ◽  
Specific Retention ◽  
5Xfad Mice ◽  
The Brain

AbstractErgothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner.

The design and synthesis of novel orally active inhibitors of AP-1 and NF-κB mediated transcriptional activation. SAR of In vitro and In vivo studies

2003 ◽  
Vol 13 (22) ◽  
pp. 4077-4080 ◽  
Author(s):  
Moorthy S.S. Palanki ◽  
Paul E. Erdman ◽  
Minghuan Ren ◽  
Mark Suto ◽  
Brydon L. Bennett ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
In Vivo Studies ◽  
Design And Synthesis ◽  
Orally Active

Design, synthesis and characterization of hydroxyapatite-chitosan nanocomposite radiolabelled with 153Sm as radiopharmaceutical for use in radiosynovectomy

2019 ◽  
Vol 108 (1) ◽  
pp. 57-65
Author(s):  
Sima Attar Nosrati ◽  
Robabeh Alizadeh ◽  
Seyed Javad Ahmadi ◽  
Mostafa Erfani
Keyword(s):  
Chemical Structure ◽  
Therapeutic Agent ◽  
Radiochemical Purity ◽  
Saline Solution ◽  
Wild Type ◽  
Design Synthesis ◽  
Physiochemical Properties

Abstract The aim of the present study was to introduction of hydroxyapatite/chitosan nanocomposite as a new radiosynovectomy agent with excellent properties. In this work, the nanocomposite was prepared through a reliable method and characterized using different techniques to elucidate its chemical structure and physiochemical properties. The prepared nanocomposite was successfully radiolabeled with 153Sm under optimal conditions and with high radiolabelling yield (99 %). The radiochemical purity of the prepared radiopharmaceutical was found to be >99 % as determined by ITLC technique. In vitro stability studies in saline solution and in human serum showed that the radiolabeled nanocomposite retained its stability for at least 6 days. The biodistribution and imaging studies in wild-type rats revealed high retention of the agent into the synovial joints of the knee even at 96 h post-injection, thereby indicating excellent in vivo stability of 153Sm labeled hydroxyapatite-chitosan nanocomposite. Therefore, the prepared radiopharmaceutical would be a potential therapeutic agent for use in radiosynovectomy procedure.

Nanocarriers for Vaccine and Gene Delivery Application

2018 ◽  
pp. 381-414 ◽  
Author(s):  
Behiye Şenel ◽  
Gülay Büyükköroğlu
Keyword(s):  
Genetic Material ◽  
Biological Properties ◽  
Target Site ◽  
Inorganic Nanoparticles ◽  
In Vivo Studies ◽  
Polymeric Systems ◽  
Design And Synthesis ◽  
Vaccine Antigens

Nanocarriers with various compositions and biological properties are frequently used systems for in-vitro/in-vivo vaccination and gene transfer. In recent years, developments in nanotechnology have focused on the design and synthesis of nanocarriers that have new properties and can be modified for gene and vaccine delivery. In the favorable results obtained from in-vivo studies performed, they increase interest in these developments and pave the way for their therapeutic use. Nanocarriers have become increasingly important because they can stabilize vaccine antigens and serve as adjuvants, with the advantage of easily transporting genetic material to the target site. In nanocarriers, the molecules involved are adsorbed to the surface or encapsulated in particulates. At the same time, surface modification of nanoparticles allows these systems to carry cargo molecules easily to target site. Among the most studied nanocarriers, lipidic and polymeric systems dendrimers, inorganic nanoparticles, cyclodextrins, cell penetration peptides, and ISCOMs are attracting attention.

Design and synthesis of specific colivelin derivatives for in vitro and in vivo studies

2011 ◽  
Author(s):  
Myrta Kostomoiri ◽  
Christos Zikos ◽  
Dimitra Benaki ◽  
Jiřina Slaninová ◽  
Ioannis Pirmettis ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Design And Synthesis

scholarly journals Design and Synthesis of Novel Thiazolo[5,4-d]Pyrimidine Derivatives with High Affinity for Both the Adenosine A1 and A2A Receptors, and Efficacy in Animal Models of Depression

2021 ◽  
Vol 14 (7) ◽  
pp. 657
Author(s):  
Flavia Varano ◽  
Daniela Catarzi ◽  
Erica Vigiani ◽  
Diego Dal Ben ◽  
Michela Buccioni ◽  
...  
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Docking Studies ◽  
In Vivo Studies ◽  
A2a Receptors ◽  
Design And Synthesis ◽  
Sucrose Preference Test ◽  
New Compounds

New compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8–10, 13, 18–19) were characterized by nanomolar and subnanomolar binding affinities for the hA1 and the hA2A AR, respectively. Results of molecular docking studies supported the in vitro results. The 2-(2-fluorobenzyl)-5-(furan-2yl)-thiazolo[5,4-d]pyrimidin-7-amine derivative 18 (hA1 Ki = 1.9 nM; hA2A Ki = 0.06 nM) was evaluated for its antidepressant-like activity in in vivo studies, the forced swimming test (FST), the tail suspension test (TST), and the sucrose preference test (SPT) in mice, showing an effect comparable to that of the reference amitriptyline.

scholarly journals Design and Synthesis of 2-Mercapto Benzoxazole coupled Benzyl Triazoles as Anti-inflammatory Agents Targeting COX-2 Enzyme

2020 ◽  
Vol 32 (12) ◽  
pp. 3209-3218
Author(s):  
K. Praveen Kumar ◽  
Y. Prashanthi ◽  
G. Rambabu ◽  
Md. Ataur Rahman ◽  
J.S. Yadav
Keyword(s):  
Chemical Space ◽  
Biological Evaluation ◽  
Inflammatory Activity ◽  
Design Synthesis ◽  
Standard Drug ◽  
Design And Synthesis ◽  
Cox 2 ◽  
Anti Inflammatory

In this study, we report the design, synthesis and the biological evaluation of 19 analogues of 2-mercapto benzoxazole coupled benzyl triazoles (BOTs) based on analysis of the binding site and literature of chemical space. These BOTs were evaluated both in vitro and in vivo for their anti-inflammatory activity. Eleven compounds showed less than 10 μM in vitro COX-2 enzyme activities. The most potent analogue among the BOT analogues were BOT15, BOT3 and BOT19 with IC50 3.40 μM, 4.50 μM and 4.57 μM respectively against COX-2. The in vivo anti-inflammatory activity of two BOTs has significantly higher than that of standard drug, ibuprofen. 2-Mercapto benzoxazole coupled benzyl triazoles (BOTs) were also tested for their antioxidant capacity and proved to be an as active scavenger, better than ascorbic acid.

Design and Synthesis of a Biocompatible 1D Coordination Polymer as Anti-Breast Cancer Drug Carrier, 5-Fu: In Vitro and in Vivo Studies

2018 ◽  
Vol 10 (21) ◽  
pp. 17594-17604 ◽  
Author(s):  
Mahsa Rezaei ◽  
Alireza Abbasi ◽  
Rassoul Dinarvand ◽  
Mahmood Jeddi-Tehrani ◽  
Jan Janczak
Keyword(s):  
Breast Cancer ◽  
Coordination Polymer ◽  
Drug Carrier ◽  
In Vivo Studies ◽  
Cancer Drug ◽  
Design And Synthesis ◽  
1D Coordination Polymer

RP-HPLC-UV-ESI-MS phytochemical analysis of fruits of Conocarpus erectus L.

2014 ◽  
Vol 68 (10) ◽  
Author(s):  
El-Sayed Abdel-Hameed ◽  
Salih Bazaid ◽  
Mohamed Shohayeb
Keyword(s):  
Antioxidant Properties ◽  
Reversed Phase ◽  
In Vivo Studies ◽  
Phytochemical Analysis ◽  
Meoh Extract ◽  
Esi Ms ◽  
Conocarpus Erectus ◽  
Rp Hplc

AbstractPrevious work revealed that the defatted methanol (MeOH) extract of fruits of Conocarpus erectus L. (Combretaceae family) exhibited antioxidant, antibacterial and anti-cancer activities. In further studies of this valuable plant, the defatted MeOH extract of C. erectus fruits was subjected to chromatographic fractionation in a silica gel glass column followed by reversed-phase high-performance liquid chromatography-ultraviolet-electrospray ionisation spectrometry analysis (RP-HPLC-UV-ESI-MS). The major and sharp peaks in each sample were identified or tentatively identified based on matching with some standard compounds and a review of the literature. Ellagic acid, vescalagin/castalagin isomer and di-(hexahydroxy diphenoyl) galloyl hexose isomer were tentatively identified as major components with many hydrolysable types of tannins on the basis of a comparison of its mass patterns with relevant items in the literature. Gallic acid, kaempferol 3-O-β-d-glucopyranoside and quercetin 3-O-β-d-glucopyranoside were identified on the basis of matching retention time (t R) and mass spectra with the standards. Polymethoxylated flavonoid isomers were also tentatively identified. The antioxidant properties of all samples were found to be associated with the total content of phenolic compounds. This may be considered as the first detailed phytochemical report in identifying the phytochemicals in C. erectus fruits. Due to the high antioxidant activity exhibited by both the crude MeOH extract and its fractions, it could be used as an effective natural antioxidant after further in vitro and in vivo studies.

Sign in / Sign up

Export Citation Format

Share Document