Distribution behavior of astatine: Solvent extraction and back extraction

The distribution behavior of astatine was studied at tracer concentrations and over a wide range of carrier iodide concentration in both solvent extraction and back extraction processes. Astatine compounds were extracted instantly into the organic solvent, CS₂ from the carrier free and carrier iodide containing solutions. Back extraction of astatine with various NaOH solutions followed by solvent extraction caused the hydrolysis of astatine. The distribution behavior of astatine was explained by the extraction reaction schemes.     

Improved and Scalable Synthetic Route to the Synthon 17-β-(2-Carboxyethyl)-1,3,5(10)-estratriene: An Important Intermediate in the Synthesis of Bone-Targeting Estrogens

An improved, highly scalable methodology for the multigram-scale preparation of an important synthon, 17-β-(2-carboxyethyl)-1,3,5(10)-estratriene, is described. Previous approaches have failed to provide useful quantities of the analytically pure product because of facile retro-Michael breakdown of the β-alkoxy carbonyl precursors during workup and isolation operations. The synthetic approach described herein has been designed specifically to sidestep this problematic breakdown process. This new scalable method of preparation overcomes a major hurdle in the exploration of structure–activity relationships centered around novel estradiol derivatives with bone-targeting properties and also provides a scalable process for subsequent developmental work.     

Identification of Novel Natural Inhibitors to Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for Cancer Treatment

Targeting the serine biosynthesis pathway enzymes has turned up as a novel strategy for anti-cancer therapeutics. 3- Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme that catalyzes the conversion of 3-Phosphoglyceric acid (3-PG) into 3-Phosphohydroxy pyruvate (3-PPyr) in the first step of serine synthesis pathway and perform a critical role in cancer progression. PHGDH has been reported to be overexpressed in different types of cancers and emerged as a novel target for cancer therapeutics. During this study, virtual screening tools were used for the identification of inhibitors of PHGDH. A library of phenolic compounds was docked against two binding sites of PHGDH using Molegro Virtual Docker (MVD) software. Out of 169 virtually tested compounds, Salvianolic acid C and Schizotenuin F possess good binding potential to co-factor binding site of PHGDH while Salvianolic acid I and Chicoric acid were identified as the best binding compounds toward the substrate binding site of PHGDH. The top selected compounds were evaluated for different physiochemical and ADMET properties, the obtained results showed that none of these hit compounds violated the Pfizer Rule and they possess acceptable ADMET profiles. Further, a commercially available hit compound, Chicoric acid, was evaluated for its anti-cancer potential against PHGDH-expressing gastric cancer cell lines (MGC-803 and SGC-7901) as well as cell lines with low expression of PHGDH (MCF-7 and MDA-MB2-31), which demonstrated that Chicoric acid possesses selective cytotoxicity toward PHGDH expressing cancer cell lines. Thus, this study has unveiled the potential of phenolic compounds, which could serve as novel candidates for the development of PHGDH inhibitors as anti-cancer agents.     

An efficient synthesis of 3,5‐dimethoxyhomophthalic acid,a key intermediate for synthesis of natural isocoumarins

3,5‐Dimethoxyhomophthalic acid was prepared efficiently in three steps, from 3,5‐dimethoxybenzyl bromide via rhodium‐catalyzed direct carbonylation to 3,5‐dimethoxyphenylacetic acid followed by successive o‐formylation and oxidation. Isocoumarins related to agrimonolide and achlisocoumarin 1 were prepared in single step by condensation of the homophthalic acid with appropriate acid chlorides.     

Iron salts catalyzed synthesis of β-N-substituted aminoacrylates

The direct condensation of amines with β-ketoesters to produce functional enamine derivatives has been investigated with iron Lewis acid catalysts. FeCl₃·6H₂O shows good catalytic activity and makes possible the chemo- and stereoselective formations of (Z)-enamine derivatives from aliphatic and aromatic primary amines under mild conditions.     

Highly selective artificial gel antibodies for detection and quantification of biomarkers in clinical samples. I. Spectrophotometric approach to design the calibration curve for the quantification

High selectivity of a biomarker is a basic requirement when it is used for diagnosis, prognosis and treatment of a disease. The artificial gel antibodies, which we synthesise by a molecular imprinting method, have this property not only for proteins, but also for bioparticles, such as viruses and bacteria. However, diagnosis of a disease requires not only that the biomarker can be “fished out” from a body fluid with high selectivity, but also that its concentration in the sample can rapidly be determined and preferably by a simple technique. This paper deals primarily with the development of a spectrophotometric method, which is so simple and fast that it can be used with advantage in a Doctor's Office. The development of this method was not straight‐forward. However, by modifications of the performance of these measurements we can now design standard curves in the form of a straight line, when we plot the true (not the recorded “apparent” absorption) against known protein concentrations. In an additional publication (see the following paper in this issue of JSS) we show an application of such a plot: determination of the concentration of albumin in serum and cerebrospinal fluid from patients with neurological disorders to investigate whether albumin is a biomarker for these diseases.     

Template polymerization of aniline in presence of poly(acrylamide-<Emphasis Type="Italic">co</Emphasis>-maleic acid) for preparation of conductive polymers

In the present work new conductive nanostructures based on poly (acrylamide-co-maleic acid) (PAAMA) and polyaniline were prepared. The template polymerization of aniline was conducted in the aqueous solution of PAAMA with different ratios (w/w%) of aniline to polyacid. The prepared composite was characterized by FTIR and UV–Vis spectroscopy, SEM, electrical conductivity measurements and solubility tests.     

X-ray absorption spectroscopic characterization of the molybdenum site of Escherichia coli dimethyl sulfoxide reductase

Structural studies of dimethyl sulfoxide (DMSO) reductases were hampered by modification of the active site during purification. We report an X-ray absorption spectroscopic analysis of the molybdenum active site of Escherichia coli DMSO reductase contained within its native membranes. The enzyme in these preparations is expected to be very close to the form found in vivo. The oxidized active site was found to have four Mo-S ligands at 2.43 A, one Mo=O at 1.71 A, and a longer Mo-O at 1.90 A. We conclude that the oxidized enzyme is a monooxomolybdenum(VI) species coordinated by two molybdopterin dithiolenes and a serine. The bond lengths determined for E. coli DMSO reductase are very similar to those determined for the well-characterized Rhodobacter sphaeroides DMSO reductase, suggesting similar active site structures for the two enzymes. Furthermore, our results suggest that the form found in vivo is the monooxobis(molybdopterin) species.