ketones

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule targeting drug eribulin on different stages of metastasis in triple negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells providing foundation for the combination therapy. Mechanistically, AURKA inhibition induced cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but...

A simple and versatile method for the synthesis of 1,5-benzodiazepines is via condensation of o-phenylenediamines (OPDA) and ketones in the presence of catalytic amount of H-MCM-22 using acetonitrile as solvent at room temperature. In all the cases, the reactions are highly selective and are completed within 1–3 h. The method is applicable to both cyclic and acyclic ketones without significant differences. The reaction proceeds efficiently under ambient conditions with good-to-excellent yields.

A simple and versatile method for the synthesis of 1,5-benzodiazepines is via condensation of o-phenylenediamines (OPDA) and ketones in the presence of catalytic amount of H-MCM-22 using acetonitrile as solvent at room temperature. In all the cases, the reactions are highly selective and are completed within 1–3 h. The method is applicable to both cyclic and acyclic ketones without significant differences. The reaction proceeds efficiently under ambient conditions with good-to-excellent yields.

Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disease (AD). Little is known about the implication of the brain's two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100...

Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a

A microbial resolution of chiral secondary alcohols with whole cells of Nocardia corallina B-276 was studied. Racemic alky- laryl carbinols were resolved into the corresponding (R)-compounds in good yields with > 99% enantiomeric excess. This enantioselective oxidation gives ketones in 38-42 % yields and they could be recycled to the bioseparation process. This is a new application of this micro- organism in organic chemistry.

The aim of this review article is to analyze the current literature in matter of therapeutic ketosis and its successful clinical applications in diabetes type I and II, thus paving the road towards a wider and safer use of this metabolic approach in these patients.

The band origins and transitions of weak vibrational modes developed in the 3500 cm−1 region of polylactide (PLA) spectra during crystallization are investigated. The band assignment to the OH stretching mode of terminal hydroxyls is unlikely because the trace amount of chain-ends is negligible considering the long chain of high molecular weight polymer. The band intensity can be enhanced for quantitative study by increasing the sample film thickness. The results show that the transition patterns of these bands mimic those of C=O stretching modes. Therefore, these are assigned to CXO overtones. Two bands associated with crystalline and amorphous characteristics are revealed during cold crystallization. The crystalline C=O bands of PDLA and its stereocomplex counterpart are located at 3510 cm−1 and 3482 cm−1, respectively, indicating a weaker C=O bond in the latter crystal structure. Two-dimensional Fourier transform infrared (2D-FT-IR) correlation spectroscopy is then applied to stu...

Large amounts of hydrocarbons accumulate during vitellogenesis in the developing basal oocytes of the German cockroach Blattella germanica (L.), and all ovarian hydrocarbons are deposited into an egg case (ootheca) during oviposition. Hydrocarbons are not synthesized by the ovaries, but are delivered by hemolymph lipoproteins and accumulate within the basal oocytes. A native B. germanica hydrocarbon, [(3)H]3,11-dimethylnonacosane, injected into adult females of various ages, was taken up by the ovaries in relation to oocyte growth. Ovarian uptake of the hydrocarbon was low in day 0-1 females, increased dramatically between days 3 and 6 and declined sharply through oviposition on day 8-9; ovarian uptake of the hydrocarbon was low during a 21-day pregnancy that followed. [1-(14)C]Propionate, which becomes incorporated into methyl-branched hydrocarbons, was injected into 5-day-old vitellogenic females to monitor the de novo biosynthesis of hydrocarbons and the time course of hydrocarbo...

Effects of feeding a dry glycerin product (minimal 65% of food grade glycerol, dry powder) to 39 multiparous Holstein dairy cows (19 control and 20 glycerin-supplemented; lactation number = 2.2 +/- 1.3 SD) on feed intake, milk yield and composition, and blood metabolic profiles were investigated. Dry glycerin was fed at 250 g/d as a top dressing (corresponding to 162.5 g of glycerol/d) to the common lactating total mixed ration from parturition to 21 d postpartum. Individual milk was sampled from 2 consecutive milkings weekly and analyzed for components. Blood was sampled from the coccygeal vein at 4, 7, 14, and 21 (+/-0.92, pooled SD) d in milk and analyzed for urea nitrogen, glucose, insulin, nonesterified fatty acids, and beta-hydroxybutyrate. Urine was tested for the acetoacetate level weekly by using Ketostix. Average feed intake, milk yield and components, blood metabolites, and serum insulin concentrations were not affected by dry glycerin supplementation. Glycerin-supplement...

Polyene cyclization of the titled compounds under catalysis with AlCl(3)/SnCl(4) gave rise to the corresponding polycyclic products, many of which were structurally highly unexpected, and thus, individual X-ray analysis was required to finalize the structural identification. Mechanistically, an unusual 1,2-hydride shift is proposed to elucidate the product formation.

The morphology of poly(aryl-ether-ether-ketone) (PEEK) has been studied using optical microscopy (at room temperature and at elevated temperatures), small-angle light scattering (H v and V v ), transmission electron microscopy (bright field, dark field, and selected area electron ...

A previous analysis by GC−MS, TLC, and FT-IR spectroscopy indicated a diterpene hydrocarbon and a diterpene ketone from the paracloacal glands of adult male, but not female, Chinese alligators, Alligator sinensis Fauvel (Crocodilia, Reptilia). 1 The molecular weight of the ...

OBJECTIVE: The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in ...

The oral bioavailability of a compound is a crucial factor in its success or failure as a therapeutic agent, particularly given the convenience of this route of administration. There are two main mechanisms of absorption from the GI tract: passive diffusion and carrier mediated transport. The ...

A high-performance liquid chromatographic method designed to analyse effluents from perfused organs is described. In the case of rat liver, compounds released by the liver are readily separated and quantitated, using a strong cation exchanger (Aminex HPX 87H), two detectors connected in series (ultraviolet detector at 210 nm and refractive index detector), and by optimizing the concentration of sulphuric acid in the mobile phase. Chromatographic conditions described in the present work enable the quantitation, in a single run, of metabolites derived from the tricarboxylic acid cycle, glycolysis, ketogenesis, adenine nucleotides catabolism and ethanol oxidation. The advantage of this method stems from its ease of implementation, sensitivity and flexibility.