N-heterocycles, namely 1,2,4-oxadiazoles and 2,6 disubstituted pyrimidin-4-ones, have been synthesised in one pot via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids under metal-free conditions.

Purpose: To determine whether deuterated water (HDO) generated from the metabolism of [ 2 H 7 ]glucose is a sensitive biomarker of cerebral glycolysis and oxidative flux. Methods: A bolus of [ 2 H 7 ]glucose was injected through the tail vein at 1.95 g/kg into Sprague-Dawley rats. A 2 H surface coil was placed on top of the head to record 2 H spectra of the brain every 1.3 minutes to measure glucose uptake and metabolism to HDO, lactate, and glutamate/glutamine. A two-point Dixon method based on a gradient-echo sequence was used to reconstruct deuterated glucose and water (HDO) images selectively. Results: The background HDO signal could be detected and imaged before glucose injection. The 2 H NMR spectra showed arrival of [ 2 H 7 ]glucose and its metabolism in a time-dependent manner. A ratio of the HDO to glutamate/glutamine resonances demonstrates a pseudo-steady state following injection, in which cerebral metabolism dominates wash-in of HDO generated by peripheral metabolism. Brain spectroscopy reveals that HDO generation is linear with lactate and glutamate/glutamine appearance in the appropriate pseudo-steady state window. Selective imaging of HDO and glucose is easily accomplished using a gradient-echo method. Conclusion: Metabolic imaging of HDO, as a marker of glucose, lactate, and glutamate/glutamine metabolism, has been shown here for the first time. Cerebral glucose metabolism can be assessed efficiently using a standard gradient-echo sequence that provides superior in-plane resolution compared with CSI-based techniques. K E Y W O R D S [ 2 H 7 ]glucose, brain, DMRI, HDO, metabolism 1 | INTRODUCTION Glucose is the principal source of energy in the brain, and its dynamic uptake and use remain a key topic after decades of research. Metabolic imaging using MR-based methods has traditionally been limited to 1 H-based spectroscopic detection of metabolites through CSI or single-voxel spectroscopy. 1,2 Although these methods have been of immense How to cite this article: Mahar R, Zeng H, Giacalone A, Ragavan M, Mareci TH, Merritt ME. Deuterated water imaging of the rat brain following metabolism of [ 2 H 7 ]glucose.

The bioassay guided fractionation of methanolic extract of Murraya koenigii (L.) Spreng. leaves resulted in the isolation of seven pyranocarbazoles. These were evaluated against four bacterial strains and ten Candida sp. including two matched pair of fluconazole sensitive/resistant clinical isolates. Out of seven, three i.e. Koenine (mk279), Koenigine (mk309) and Mahanine (mk347) exhibited significant antibacterial activity MIC90 3.12-12.5 μg/mL against bacterial strains Streptococcus aureus and Klebsiella pneumonia compared with standard drug Kanamycin MIC90 12.5 μg/mL. However, only mk309 was found active against variety of Candida species MIC90 12.5-100 μg/mL. It was observed that hydroxylation at C-6 and C-7 positions in the studied pyranocarbazoles activate the bioactivity. Simultaneously, decrease in Log P value compares with -H and -O-CH3 substituted derivatives. The study is focused on selective antifungal and antibacterial activity of pyranocarbazoles on bacterial strains S. aureus, K. pneumonia and variety of Candida species with structure activity relationship observations.

Increased glucose uptake and aerobic glycolysis are striking features of many cancers. These features have led to many techniques for screening and diagnosis, but many are expensive, less feasible or have harmful side-effects. Here, we report a sensitive 1 H/ 2 H nMR method to measure the kinetics of lactate isotopomer and HDO production using a deuterated tracer. To test this hypothesis, HUH-7 hepatocellular carcinoma and AML12 normal hepatocytes were incubated with [ 2 H 7 ]glucose. 1 H/ 2 H nMR data were recorded for cell media as a function of incubation time. The efflux rate of lactate-CH 3 , lactate-cH 2 D and lactate-cHD 2 was calculated as 0.0033, 0.0071, and 0.0.012 µmol/10 6 cells/min respectively. Differential production of lactate isotopomers was due to deuterium loss during glycolysis. Glucose uptake and HDo production by HUH-7 cells showed a strong correlation, indicating that monitoring the HDO production could be a diagnostic feature in cancers. Deuterium mass balance of [ 2 H 7 ]glucose uptake to 2 H-lactate and HDO production is quantitatively matched, suggesting increasing HDO signal could be used to diagnose Warburg (cancer) metabolism. Measuring the kinetics of lactate isotopomer and HDO production by 1 H and 2 H MR respectively are highly sensitive. increased t 1 of 2 H-lactate isotopomers indicates inversion/ saturation recovery methods may be a simple means of generating metabolism-based contrast.

The purpose of this study was to investigate hyperpolarization and in vivo imaging of [ 15 N]carnitine, a novel endogenous MRI probe with long signal lifetime. Methods: L-[ 15 N]carnitine-d 9 was hyperpolarized by the method of dynamic nuclear polarization followed by rapid dissolution. The T 1 signal lifetimes were estimated in aqueous solution and in vivo following intravenous injection in rats, using a custom-built dual-tuned 15 N/ 1 H RF coil at 4.7 T. 15 N chemical shift imaging and 15 N fast spin-echo images of rat abdomen were acquired 3 minutes after [ 15 N]carnitine injection. Results: Estimated T 1 times of [ 15 N]carnitine at 4.7 T were 210 seconds (in H 2 O) and 160 seconds (in vivo), with an estimated polarization level of 10%. Remarkably, the [ 15 N]carnitine coherence was detectable in rat abdomen for 5 minutes after injection for the nonlocalized acquisition. No downstream metabolites were detected on localized or nonlocalized 15 N spectra. Diffuse liver enhancement was detected on 15 N fast spin-echo imaging 3 minutes after injection, with mean hepatic SNR of 18 ± 5 at a spatial resolution of 4 × 4 mm. Conclusion: This study showed the feasibility of hyperpolarizing and imaging the biodistribution of HP [ 15 N]carnitine.