Accuracy of SenseWear Pro2 armband to predict resting energy expenditure in childhood obesity.

OBJECTIVE: We evaluate the accuracy of the SenseWear Pro2 Armband (SWA) in estimating resting energy expenditure (REE) in children and adolescents with obesity, using indirect calorimetry (IC) as a reference. DESIGN AND METHODS: REE was assessed using both the SWA and IC in 40 obese subjects (26 M/14 F, age 11.5±2.57 years, z-score BMI 3.14±0.53). The agreement between methods was assessed by the Bland-Altman procedure. The relationship between REE assessments and patients' characteristics was also analyzed. RESULTS: SWA- and IC-derived estimates of REE showed a significant correlation (r=0.614; P<0.001), but the SWA overestimated mean REE by 13% (P<0.001). Age and kg of fat-free mass (kgFFM) were significantly correlated with both REE estimation by SWA (r=0.434 and r=0.564; respectively) and IC (r=0.401 and r=0.518; respectively). Only kgFFM was demonstrated to be the main predictor factor of REE variability (r2 79% SWA; 75% IC). CONCLUSIONS: The SWA overestimated mean REE in childhood obesity, suggesting that the SWA and IC are not yet interchangeable methods. This would require improving the SWA by developing better algorithms for predicting REE and, probably, bias in each individual REE could be reduced by an adjustment for subjects' kgFFM

Application of (S,S)-Pentacycloundecane bis(4-Phenyloxazoline) as a Novel Chiral Ligand for Catalysis of the Asymmetric Diels-Alder Reaction of Cyclopentadiene with 3-Acryloyl-2-oxazolidinone

The synthesis of the novel C1 symmetric (S,S)-pentacycloundecane bis(4-phenyloxazoline) ligand 5 and its evaluation as a chiral Lewis acid catalyst in the benchmark asymmetric Diels-Alder reaction between 3-acryloyloxazolidin-2-one (6) and cyclopentadiene (7) is reported. From the various metal salts screened the anhydrous magnesium perchlorate complex emerged as the best catalyst. The endo-cycloadduct product 8 was afforded in 81% enantiomeric excess with an endo:exo ratio of 98:2. An extensive screening of various metal ions as complexing agents was performed and is also reported.Keywords: Pentacycloundecane, oxazolines, chiral catalysis, Diels-Alder reactionPDF and Supplementry file attache

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors

Front Cover: Solid Phase Synthesis of Sulfonimidamide Pseudopeptides and Library Generation (Eur. J. Org. Chem. 25/2020)

The Front Cover shows the combined world of solid‐phase peptide synthesis and sulfur chemistry on a background of a sulfur landscape. A peptide chain attached to a polymer resin is functionalized through formation of a sulfonamide and the magic touch of triphenylphosphine dichloride. The resulting sulfonimidamide pseudopeptides are thereafter released from the resin. The method allows easy generation of novel chemical libraries, useful in drug discovery. Graphic design by Andrea Benediktsdottir. More information can be found in the Full Paper by P. K. Chinthakindi, A Benediktsdottir, A. Sandström et al

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides <i>via</i> three component SuFEx type reaction

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors. The β-aminoethane sulfonamides were obtained through sequential Michael addition of amines to α,β-unsaturated ethenesulfonyl fluorides followed by further DBU mediated sulfur(vi) fluoride exchange (SuFEx) reaction with amines at the S–F bond