Search results for "Hydrazines"
showing 10 items of 62 documents
Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats.
2010
Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronate, an inhibitor of L-carnitine biosynthesis, or their combination on the development of hypertension-related complications in Dahl salt-sensitive (DS) rats fed with a high salt diet. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Experimental animals were divided into five groups and treated for 8 weeks with vehicle (water; n = 10), L-carnitine (100 mg/kg, n = 10), mildronate (100 mg/kg, n = 10) or a combination of L-carnitine and mildronate at…
Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.
2014
The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) e…
Carnitine transport into muscular cells. inhibition of transport and cell growth by mildronate
2000
Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is found in dairy and meat products, but is also biosynthesized from lysine and methionine via a process that, in rat, takes place essentially in the liver. After intestinal absorption or hepatic biosynthesis, carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle. In skeletal muscle, carnitine concentration was found to be 50 times higher than in the plasma, implicating an active transport system for carnitine. In this study, we characterized this transport in isolated rat myotubes, established mouse C2C12 myoblastic cells, and …
Effect of inhibiting carnitine biosynthesis on male rat sexual performance.
2008
l-carnitine has a documented role as a cofactor in cellular energy metabolism and fatty acid beta-oxidation pathways and it has also been considered to function in reproductive biology. We investigated whether decreasing concentrations of L-carnitine using an inhibitor of its biosynthesis, mildronate (3-(2,2,2-trimethylhydrazinium)-propionate), would influence the sexual behavior or sperm quality in male rats. Mildronate treatment induced a significant decrease in carnitine concentration and an increase in gamma-butyrobetaine (GBB) concentration in both plasma and testes extracts. However, the expression of carnitine palmitoyltransferase I in testes and testosterone concentration in plasma …
Enhancement of activities relative to fatty acid oxidation in the liver of rats depleted of l-carnitine by d-carnitine and a γ-butyrobetaine hydroxyl…
1995
Abstract This study was designed to examine whether the depletion of l -carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received d -carnitine for 2 days and 3-(2,2,2-trimethylhydrazinium)propionate (mildronate), a non-competitive inhibitor of γ-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to …
Influence of different parameters on drug release from hydrogel systems to a biomembrane model. Evaluation by differential scanning calorimetry techn…
2000
A comparative study on the drug release capacity of four water swellable polymeric systems was carried out by differential scanning calorimetry (DSC). The polymeric systems chosen were alpha,beta-polyaspartahydrazide (PAHy) crosslinked by glutaraldehyde (GLU) (PAHy-GLU) or by ethyleneglycoldiglycidylether (EGDGE), (PAHy-EGDGE), polyvinylalcohol (PVA) crosslinked by glutaraldehyde (PVA-GLU) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) by gamma irradiation (PHEA-gamma matrices). The degree of crosslinking for PAHy-GLU, PAHy-EGDGE and PVA-GLU samples was about 0.4 and 0.8. These hydrogels were characterized as free of drugs and were loaded with diflunisal (DFN) (approximately 2.5%…
Synthesis and analysis of activity of a potential anti-melanoma prodrug with a hydrazine linker
2013
A potential anti-melanoma prodrug containing a phenolic activator, a hydrazine linker, and a nitrogen mustard effector - (N-{4-[bis-(2-chloroethyl)amino]benzoyl}-N'-(4-hydroxybenzyl)hydrazine) has been synthesized in seven steps. Spectrophotometric measurements of its oxidation by tyrosinase showed a rapid increase of absorbance at 337 nm. HPLC analysis demonstrated that two major products were formed. However, during the reaction one of the products was converted into the other. The stable product with a maximum of absorption at 337 nm was isolated and identified as 5,6-dihydroxy-1H-indazol-1-yl 4-[bis-(2-chloroethyl)amino]benzoate. It was formed by a cyclization of the enzymatically gener…
Improved Regioselectivity in Pyrazole Formation through the Use of Fluorinated Alcohols as Solvents: Synthesis and Biological Activity of Fluorinated…
2008
The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity. Fil: Fustero, Santos. Universidad de Valencia; España Fil…
Synthesis, in vitro activity, and three-dimensional quantitative structure-activity relationship of novel hydrazine inhibitors of human vascular adhe…
2010
Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those s…
In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents
2012
Abstract Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum , Leishmania infantum , Trypanosoma brucei , and Trypanosoma cruzi , resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds