scholarly journals Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

2019 ◽  
Vol 7 (3) ◽  
pp. 39 ◽  
Author(s):  
Daniela García-Alonso ◽  
Dan Morgenstern-Kaplan ◽  
Ariel Cohen-Welch ◽  
Jair Lozano-Cuenca ◽  
Jorge López-Canales
Keyword(s):  
In Vivo Studies ◽  
Vasorelaxant Effect ◽  
Cardiovascular Side Effects ◽  
Clinical Benefits ◽  
Calcium Activated Potassium Channels ◽  
Vasodilating Activity ◽  
Treatment Of Obesity ◽  
Derivatives Of ◽  
Vasodilating Effect

Anorexigenics are compounds capable of reducing or suppressing appetite. Their three main types act on different neurotransmitters, either norepinephrine, serotonin or a combination of both. Among the drugs that act on norepinephrine are fenproporex, amfepramone and clobenzorex. Derivatives of the thyroid hormone triiodothyronine have also been associated with weight loss and used as a controversial treatment for obesity, despite their known cardiovascular side effects. Recent data suggest a possible vasodilating effect for these four substances that might be beneficial in a subset of patients. Herein we performed a systematic review of the literature (with emphasis on recent reports) to determine the implications and mechanisms of the vasodilating effects of some anorectics, specifically fenproporex, clobenzorex, amfepramone and triiodothyronine. Data analysis showed these four drugs to be vasodilating agents for rat aortic rings. The different mechanisms of action include endothelium-dependent vasodilation via activation of the NO-cGMP-PKG pathway and the opening of calcium-activated potassium channels. The finding of vasodilating activity indicates a potential role for some anorexigenic drugs in the treatment of obesity in hypertensive patients. Further in vivo studies are needed to test the clinical benefits of these four drugs.

Two in one: bifunctional derivatives of trolox acting as antimalarial and antioxidant agents

2020 ◽  
Vol 12 (20) ◽  
pp. 1845-1854
Author(s):  
Florence Souard ◽  
Edwige Nicolle ◽  
Delphine Cressend ◽  
Alexis Valentin ◽  
Ahcène Boumendjel
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
In Vivo Studies ◽  
Chemical Libraries ◽  
Falciparum Strain ◽  
Antioxidant Agents ◽  
One Step ◽  
Set Up ◽  
Derivatives Of

Background: The aim of the present work was to set-up compounds that are able to act simultaneously as antimalarial and antioxidants. Trolox, a known antioxidant was chosen as a core structure to ensure the antioxidant activity and contribute to antiplasmodial effect. Results: Ten compounds were prepared in one step and evaluated on chloroquino-sensitive (3D7) and chloroquino-resistant (FcB1) strains of Plasmodium falciparum. The most active compound (3d) shows antiplasmodial activity in the range of chloroquine against chloroquino-sensitive and chloroquino-resistant P. falciparum strain. The antioxidant activity of (3d) was conducted through four tests and was found to be more potent than trolox itself and L-ascorbic acid. Conclusion: Compound (3d) can be considered as an excellent lead molecule for further in vivo studies. This study paves the way for building large chemical libraries to be investigated in the field of malaria.

scholarly journals RARE-22. THERAPEUTIC TARGETING OF PURINE METABOLISM IN DIPG

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i45-i45
Author(s):  
Ian Mersich ◽  
Biplab Dasgupta
Keyword(s):  
Cell Lines ◽  
De Novo ◽  
Treatment Strategies ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Purine Metabolism ◽  
In Vivo Studies ◽  
Molecule Inhibitor ◽  
Clinical Benefits

Abstract Diffuse intrinsic pontine glioma is a universally lethal disease primarily impacting pediatric patients. There are currently no targeted therapies increasing overall for patients with these tumors; therefore, our lab set out to elucidate metabolic dependencies in DIPG patient-derived cell lines with the ultimate goal of identifying novel therapeutic targets. Through untargeted metabolomics and gene expression analyses, we have identified the purine metabolism gene ATIC to be important for DIPG tumor cell survival and proliferation. Anti-folate drugs such as methotrexate target de novo purine biosynthesis and are used to treat other pediatric cancers; however, we have identified a small molecule inhibitor of ATIC that may offer clinical benefits over other inhibitors of this pathway. In vitro cell viability experiments have demonstrated DIPG cell lines are much more sensitive to the ATIC inhibitor relative to normal neural stem cells and glial cell lines. Furthermore, we have started in vivo studies on pre-clinical mouse models of DIPG with promising results. Treatment with the ATIC inhibitor has significantly increased overall survival relative to control and vehicle treated mice. The dosage we started at was well tolerated in these mice so we are following up on this in vivo work through dose-escalation studies as well as combination treatment strategies. Mechanistically, the ATIC inhibitor works differently than anti-folate compounds such as methotrexate; therefore we are also elucidating why cancer cells are much more sensitive to this compound.

scholarly journals STUDY OF THE AFFINITY OF N-ACYL DERIVATIVES OF 2-OXO-1-PYRROLIDINE ACETAMIDE TO THE BINDING SITE OF NMDA RECEPTOR BY MOLECULAR DOCKING METHOD

2019 ◽  
pp. 4-6
Author(s):  
A.S. Chiriapkin ◽  
A.A. Glushko ◽  
I.P. Kodonidi
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Nmda Receptor ◽  
Binding Site ◽  
Computational Method ◽  
In Vivo Studies ◽  
Docking Method ◽  
Derivatives Of ◽  
Acyl Derivatives

The search for new compounds with а high nootropic biological activity is a promising scientific direction. A modern computational method for predicting pharmacological activity of the studied compounds is the molecular docking. The aim of this work is to study the affinity of new N-acyl derivatives of 2-oxo-1-pyrrolidine acetamide to the binding site of NMDA receptor to search of new effective nootropic drugs. As objects of study, there are used the new N-acyl derivatives of 2-oxo-1-pyrrolidine acetamide, racetams, glutamate and a virtual model of NMDA receptor of organism Rattus norvegicus with an identification code 2A5S from the RCSB PDB database. The results of the computational experiment indicate the presence of high nootropic biological activity in the compounds under study. Substance 3 has the greatest affinity of the N-acyl derivatives of 2-oxo-1-pyrrolidineethanol to the binding site of NMDA receptor Thus, we consider it is appropriate to conduct pharmacological in vivo studies of these compounds for the presence of nootropic biological activity.

scholarly journals Cysteine Derivatized 99mTc-Labelled Fatty Acids as β-Oxidation Markers

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 133
Author(s):  
Theodoros Tsotakos ◽  
Charalambos Triantis ◽  
Christos Kiritsis ◽  
Aggeliki Panagiotopoulou ◽  
Dimitrios Psimadas ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Myocardial Metabolism ◽  
Radiochemical Yield ◽  
In Vivo Studies ◽  
Rapid Clearance ◽  
Derivatives Of ◽  
Heart Uptake ◽  
Donor System

With the aim of developing 99mTc-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the ω-site by cysteine through the formation of a thioether bond (Cys–FA11 and Cys–FA16). Equimolar amounts of each ligand and the [NEt4]2[Re(CO)3Br3] precursor generated the respective hexacoordinated neutral complexes in which the ligand coordinated to the metal through the SNO donor system of cysteine. The rhenium complexes were characterized by elemental analysis, IR and NMR spectroscopies. The analogous technetium-99m complexes, 99mTc–Cys–FA11 and 99mTc–Cys–FA16 were prepared by incubation of the ligand with the precursor [99mTc(CO)3(H2O)3]+ (radiochemical yield ≥98%). Their structure was established by comparative HPLC techniques. In vivo studies in mice showed high initial heart uptake for both 99mTc complexes (7.4 ± 0.53 and 7.07 ± 0.73 percentage of injected dose (%ID)/g at 1 min post injection. Rapid clearance (0.60 ± 0.02 %ID/g) was observed for 99mTc–Cys–FA11 while the clearance of the longer fatty acid 99mTc–Cys–FA16 was slower (2.31 ± 0.09 %ID/g at 15 min p.i.). Metabolite analysis study indicated that complexes were catabolized through the β-oxidation process.

scholarly journals Food phytochemicals against Helicobacter pylori

2021 ◽  
Vol 14 (1) ◽  
pp. 11-17
Author(s):  
Alexandru Mandici ◽  
◽  
Alina-Alexandra Covrig ◽  
Irina Macovei ◽  
◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Peptic Ulcers ◽  
Urease Enzyme ◽  
Bactericidal Effects ◽  
Main Culprit ◽  
Clinical Benefits ◽  
H Pylori ◽  
Different Strains

H. pylori is a widespread pathogen, being the main culprit behind gastric and peptic ulcers with possible implications in the development of gastric cancers. In vitro studies have shown that ellagic acid and derivatives present in significant amounts in fruits and leaves have moderate bactericidal effects on H. pylori, while resveratrol was noted to inhibit urease enzyme as high as 90% in different strains of H. pylori. Quercetin seems to inhibit pathogen’s VacA enzyme and kaempferol may prevent translocation of CagA, both phytochemicals being found in significant amounts in berries. In one clinical study, allicin was found to act synergically with standard antibiotic regimens. Although in vitro results seem promising, in vivo studies did not underline significant clinical benefits of phytochemicals compared to standard therapy. Therefore, further studies are needed to accurately estimate any clinical benefit of dietary phytochemicals in H. pylori infection.

Sign in / Sign up

Export Citation Format

Share Document