ABSTRACT
BACKGROUND/AIMS: Whey proteins (WP), obtained from milk after casein precipitation, represent a heterogeneous group of proteins. WP are reported to inhibit food intake in diet-induced experimental obesity; WP have been proposed as adjuvant therapy in oxidative stress-correlated pathologies. This work evaluates the effects of WP in comparison with casein, as a source of alimentary proteins, on food intake, weight growth and some indexes of oxidative equilibrium in Zucker Rats, genetically prone to obesity. METHODS: We monitored food intake and weight of Zucker Rats during the experiment, and some markers of oxidative equilibrium. RESULTS: WP induced significant decrease of food intake in comparison to casein (WP 80.41 ± 1.069 ml/day; CAS: 88.95 ± 1.084 ml/day; p < 0.0005). Body weight growth was slightly reduced, and the difference was just significant (WP 128.2 ± 6.56 g/day; CAS 145.2 ± 3.29 g/day; p = 0.049), while plasma HNE level was significantly lower in WP than in CAS (WP 41.2 ± 6.3 vs CAS 69.61 ± 4.69 pmol/ml, p = 0.007). Mild amelioration of oxidative equilibrium was indicated by a slight increase of total glutathione both in the liver and in the blood and a significant decrease of plasma 4-hydroxynonenal in the group receiving WP. CONCLUSIONS: The effect of WP on food intake and weight growth in Zucker Rats is particularly noteworthy since the nature of their predisposition to obesity is genetic; the possible parallel amelioration of the oxidative balance may constitute a further advantage of WP since oxidative stress is believed to be interwoven to obesity, metabolic syndrome and their complications.
Subject(s)
Obesity , Oxidative Stress , Animals , Eating , Humans , Obesity/drug therapy , Rats , Rats, Zucker , Whey Proteins/pharmacologyABSTRACT
On the pattern of the potent and selective butyrylcholinesterase (BChE) inhibitors ethopropazine and Astra1397, sets of quinolizidinyl derivatives of bi- and tricyclic (hetero)aromatic systems were studied as dual, or BChE-selective inhibitors. All compounds exhibited activity against both cholinesterases, but inhibition of BChE was generally stronger, with submicromolar IC50 values for most of them (e.g. 15: IC50 versus BChE=0.15 µM; SI=47). However, in a subset of quinolizidinyl derivatives of 6-hydroxycoumarin an inverted selectivity for acetylcholinesterase (AChE) was observed (e.g. 46: IC50 versus AChE=0.35 µM; SI=0.06). Docking studies furnished a sound interpretation of the observed different enzyme activity. Several of the studied compounds have shown, in the past, additional pharmacological properties (as antagonism on presynaptic muscarinic autoreceptor; inhibition of enkephaline aminopeptidase and antipsychotic activity) of some relevance in Alzheimer's disease, and may, therefore, represent hits for the development of interesting single-entity multi-target drugs.
Subject(s)
Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Quinolizidines/pharmacology , Alzheimer Disease/enzymology , Animals , Cattle , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Erythrocytes/enzymology , Models, Molecular , Molecular Structure , Quinolizidines/chemical synthesis , Quinolizidines/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Quinolizidinyl derivatives of the tricyclic systems characterizing pirenzepine and nuvenzepine, were prepared and tested as ligands for muscarinic M1, M2 and M3 receptors; 5,11-dihydro-11-[(S-lupinyl)-thioacetyl]-6H-pyrido[2,3-b][1, 4]benzodiazepin-6-one exhibited IC50 = 10 nM for M1 and 760 nM for both M2 and M3 subtypes. During the synthesis some interesting side compounds were isolated and characterized.
Subject(s)
Benzodiazepinones/chemistry , Pyridines/chemistry , Quinolizines/metabolism , Receptors, Muscarinic/metabolism , Animals , Binding, Competitive , Ligands , N-Methylscopolamine/metabolism , Pirenzepine/metabolism , Quinolizines/chemistry , Radioligand Assay , RatsABSTRACT
A small set of 9-(lupinylthio)xanthene, -thioxanthenes and alpha-(lupinylthio)diphenylmethanes was prepared and found to inhibit the angiotensin II-induced contractions of guinea pig ileum. Some of these compounds were also moderately active in vitro as tracheal relaxants and one compound was more active than aspirin against arachidonic acid-induced platelet aggregation.
Subject(s)
Angiotensin II/antagonists & inhibitors , Muscle, Smooth/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Quinolizines/chemistry , Trachea/drug effects , Adrenal Glands/drug effects , Adrenal Glands/metabolism , Animals , Binding, Competitive/drug effects , Guinea Pigs , In Vitro Techniques , Male , Muscle Contraction/drug effects , Platelet Aggregation Inhibitors/pharmacology , Rabbits , Spectrophotometry, UltravioletABSTRACT
A set of benzimidazole derivatives bearing on position 2 a tetrahydropyranyl or tetrahydrofuranyl residue was prepared and tested for antitumoral, anti HIV-1 and other pharmacological activities. While the anti-HIV activity was completely lacking, moderate antitumoral activity was found in a few compounds; particularly the 5,6-dichloro-2-(tetrahydropyran-2-yl)-benzimidazole (8) was able to inhibit the growth of 19 cell lines of humane tumors at near micromolar concentration. On the other hand compounds 4, 6-8 and 10 exhibited significant tracheal relaxant activity in vitro at concentration 3-10 micrograms/ml, thus resulting superior to theophylline and comparable to amrinone.
