Search results for "Azoles"
showing 10 items of 899 documents
Formation of Pyrazol-1,3,4-Thiadiazoles through 1,3-Dipolar Cycloadditions of 3-Thioxo-[1,2,4]-Triazepin-5-one with Nitrilimines: An Experimental and…
2009
In this work the results of experimental and computational study of the title compounds and some ancillary compounds are reported. Two bicyclic pyrazol-1,3,4-thiadiazole derivatives were synthesized by reaction between 6-dimethylaminomethylene-3-thioxo-[1,2,4]- triazepin-5-one 1 and several nitrilimines 2a-f to give corresponding spirocycloadducts 3a-f, which undergo a rapid rearrangement leading to the new bicyclic compounds, 4a-f and 5a-f. These obtained bicyclic products were characterized by 1H and 13C NMR spectroscopy and finally by X-ray crystallography. Theoretical calculations have been carried out using DFT methods to rationalize the formation of the two new bicyclic compounds. Two…
Combined heterologies for monoclonal antibody-based immunoanalysis of fluxapyroxad
2018
Nowadays, instrumental methodologies and rapid bioanalytical techniques complement each other for the analysis of toxic chemical compounds. Fluxapyroxad was commercialized a few years ago as a fungicide and today it is being used worldwide to control a variety of pests. In the present study, the development of monoclonal antibody-based immunochemical methods for the analysis of this chemical in food samples was evaluated for the first time. Novel haptens were synthesized and protein bioconjugates were prepared. High-affinity and specific monoclonal antibodies to fluxapyroxad were generated from two haptens with alternative linker tethering sites. Haptens with linker site heterology and a st…
1,5-Disubstituted 1,2,3-Triazoles as Amide Bond Isosteres Yield Novel Tumor-Targeting Minigastrin Analogs.
2021
[Image: see text] 1,5-Disubstituted 1,2,3-triazoles (1,5-Tz) are considered bioisosteres of cis-amide bonds. However, their use for enhancing the pharmacological properties of peptides or proteins is not yet well established. Aiming to illustrate their utility, we chose the peptide conjugate [Nle(15)]MG11 (DOTA-dGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH(2)) as a model compound since it is known that the cholecystokinin-2 receptor (CCK2R) is able to accommodate turn conformations. Analogs of [Nle(15)]MG11 incorporating 1,5-Tz in the backbone were synthesized and radiolabeled with lutetium-177, and their pharmacological properties (cell internalization, receptor binding affinity and specificity, pla…
Role of calcium in E-selectin induced phenotype of T84 colon carcinoma cells
2003
The adhesion of cancer cells to the endothelium during the metastatic process involves the interaction of specific cell-cell adhesion receptors on the cell surface. E-selectin on endothelial cells and sialyl Lewis X carbohydrate component on tumor cells are mainly implicated in the adhesion of colon carcinoma cells to the endothelium of target organ. In this paper we show that binding of E-selectin to T84 colon tumor cells causes approximately a twofold increase in intracellular calcium concentration. In particular, using two inhibitors of receptor operated calcium channels, CAI and SK&F 96365, we present evidences that the augmentation in cytoplasmic calcium originates from ionic influx fr…
Trehalose effects on α-crystallin aggregates
2007
alpha-Crystallin in its native state is a large, heterogeneous, low-molecular weight (LMW) aggregate that under certain conditions may progressively became part of insoluble high-molecular weight (HMW) systems. These systems are supposed to play a relevant role in eye lens opacification and vision impairment. In this paper, we report the effects of trehalose on alpha-crystallin aggregates. The role of trehalose in alpha-crystallin stress tolerance, chaperone activity and thermal stability is studied. The results show that trehalose stabilizes the alpha-crystallin native structure, inhibits alpha-crystallin aggregation, and disaggregates preformed LMW systems not affecting its chaperone acti…
Heme oxygenase-1 induction by nitric oxide in RAW 264.7 macrophages is upregulated by a cyclo-oxygenase-2 inhibitor.
2001
Unstimulated RAW 264.7 macrophages express negligible heme oxygenase-1 (HO-1) protein but incubation with the nitric oxide (NO) donor spermine nonoate (SPNO) induced HO-1 and weakly cyclo-oxygenase-2 (COX-2) protein. This effect was potentiated by coincubation with the COX-2 selective inhibitor, SC58125. Cells incubated with SPNO showed a strong increase in HO-1 mRNA levels after 4 h with a significant potentiation in the presence of SC58125, which did not modify HO-1 mRNA stability. The induction of HO-1 by NO and its potentiation by anti-inflammatory agents may play a role in inflammatory and immune responses.
The [Fe(etz)6](BF4)2 Spin-Crossover System - Part Two: Hysteresis in the LIESST Regime
1996
In the [Fe(etz)6](BF4)2 spincrossover system the iron(II) complexes occupy two nonequivalent lattice sites, sites A and B. Complexes on site A show a thermal high-spin (HS) low-spin (LS) transition at 105 K, whereas complexes on site B remain in the HS state down to 10 K. Complexes on both sites exhibit light-induced spin state conversions (LIESST) at 20 K: LS HS on site A with = 514.5 nm, and HS LS on site B with = 820 nm. The relaxation processes subsequent to the HS LS conversion on site B reveal a light-induced HSLS bistability for the complexes on site B at 70 K. The bistability as well as the absence of a thermal spin transition on site B are attributed to a thermal hysteresis for the…
Chronic peroxisome proliferator-activated receptorβ/δ agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endotheli…
2015
Endothelial dysfunction plays a key role in obesity-induced risk of cardiovascular disease. The aim of the present study was to analyze the effect of chronic peroxisome proliferator-activated receptor (PPAR)β/δ agonist GW0742 treatment on endothelial function in obese mice fed a high-fat diet (HFD).Five-week-old male mice were allocated to one of the following groups: control, control-treated (GW0742, 3 mg/kg per day, by oral gavage), HFD, HFD + GW0742, HFD + GSK0660 (1 mg/kg/day, intraperitoneal) or HFD-GW0742-GSK0660 and followed for 11 or 13 weeks. GW0742 administration to mice fed HFD prevented the gain of body weight, heart and kidney hypertrophy, and fat accumulation. The increase in …
Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.
2015
International audience; The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out so…
Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone.
2014
Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data ar…