Synthetic studies on prostaglandins: "synthesis of a new thia-PGEI analog"

A PGE1 analog, namely (±)-trans-2-(6'-carbomethoxyhexyl)-3- (E-3"-thia-1 "-octene)-4-hydroxycyclopentanone 71, has been prepared for the first time. Towards the synthesis of this compound, several synthetic approaches aimed at the preparation of the required acetylenic and E-halovinylic sulfides as building blocks were investigated. Among all the methods examined, it appeared evident that the best route to ethynyl n.pentyl sulfide 81 is via a double dehydrohalogenation of the corresponding 1,2-dibromoethyl sulfide with sodium amide in liquid ammonia. In addition, the isomerically pure E-2-iodoethenyl n.pentyl sulfide 85 is conveniently prepared in high yield and stereoselectivity by hydrozirconation-iodination of the terminal ethynyl sulfide 81. The classical hydroalumination and hydroboration reactions for the preparation of vinyl halides from alkynes gave only small yields when applied as methods towards the synthesis of 85 . The building block 2-(6'-carbomethoxyhexyl)-4-hydroxy-2- cyclopentenone (±)-1 carrying the upper side-chain of prostaglandin E 1 was prepared by a step-wise synthesis involving transformations of compounds possessing the required carbocyclic framework (see scheme 27). The synthesis proved to be convenient and gave a good overall yield of (±)-1 which was protected as the TH P-derivative 37 or the siloxy derivative 38. With the required building blocks 81 and 37 in hand, the target 1S-thia-PGE1 analog (±)-71 was prepared via the in situ higher cuprate formation-conjugate addition reaction. This method proved to be convenient and stereospecific. The standard cuprate method, involving an organocuprate reagent generated from an isolated vinyl iodide, did not work well in our case and gave a complicated mixture of products. The target compound will be submitted for assessment of bio log ical activity

Upregulation of interleukin-19 in severe asthma: a potential saliva biomarker for asthma severity

Interleukin (IL)-19, a designated IL-20 subfamily cytokine, has been implicated in inflammatory disorders including rheumatoid arthritis, psoriasis and, lately, asthma. Here, through the analysis of transcriptomic datasets of lung tissue of large asthma cohorts, we report that IL-19 expression is upregulated in asthma and correlates with disease severity. The gene expression of IL-19 was significantly higher in lung tissue from patients with severe and mild/moderate asthma compared to healthy controls. IL-19 protein level, however, was significantly higher in the blood and saliva of patients with severe asthma compared to mild/ moderate subgroups as measured by ELISA assay. IL-19 protein level was not affected by corticosteroid treatment in plasma. Our data provide insights into the potential use of IL-19 as a saliva marker for asthma severity and a potential therapeutic target

SYNTHESIS OF POTENT ANTAGONISTS FOR THE NATRIURETIC PEPTIDE CLEARANCE RECEPTOR

Objectives: The objective of this research was to design and prepare natriuretic peptide clearance receptor (NPR-C) clearance receptor antagonists with potential therapy for achondroplasia, an autosomal dominant disorder that interferes with the synthesis of the cartilage growth plate of long bones.Methods: Peptides were synthesized by the standard solid-phase peptide synthesis (SPPS) protocol on Rink resin using the N-Fmoc/t-butyl protection methodology. Biological activity of NPR-C antagonists was assessed using ATDC5 cells.Results: SPPS rapidly generated many crude compounds with purities exceeding 80%. The synthesized ligands were further purified by liquid chromatography-mass spectrometry (LC-MS), and their identities were confirmed by MS and nuclear magnetic resonance. Ligands with nanomolar potencies were obtained.Conclusion: Structure-activity relationship studies resulted in a good selection of stable, low nanomolar, and linear NPR-C antagonists

SYNTHESIS OF POTENT ANTAGONISTS FOR THE NATRIURETIC PEPTIDE CLEARANCE RECEPTOR

Objectives: The objective of this research was to design and prepare natriuretic peptide clearance receptor (NPR-C) clearance receptor antagonists with potential therapy for achondroplasia, an autosomal dominant disorder that interferes with the synthesis of the cartilage growth plate of long bones.Methods: Peptides were synthesized by the standard solid-phase peptide synthesis (SPPS) protocol on Rink resin using the N-Fmoc/t-butyl protection methodology. Biological activity of NPR-C antagonists was assessed using ATDC5 cells.Results: SPPS rapidly generated many crude compounds with purities exceeding 80%. The synthesized ligands were further purified by liquid chromatography-mass spectrometry (LC-MS), and their identities were confirmed by MS and nuclear magnetic resonance. Ligands with nanomolar potencies were obtained.Conclusion: Structure-activity relationship studies resulted in a good selection of stable, low nanomolar, and linear NPR-C antagonists

Properties of Raw Saudi Arabian Grey Kaolin Studied by Pyrrole Adsorption and Catalytic Conversion of Methylbutynol

This current article demonstrates how X-ray fluorescence spectroscopy (XRF) was employed to reveal the major constituents of a sample of natural grey Saudi kaolin. The XRF results showed that it contained 52.90 wt.% silica together with 14.84 wt.% alumina. Additionally, this paper presents a study on the effect of holding times (i.e., 6, 12, 18, and 24 h) using pyrrole adsorption and methylbutynol test reaction (MBOH) on the Saudi grey kaolin (raw material). Temperature-programmed desorption of pyrrole (pyrrole-TPD) results indicated that increases in thermal conductivity detector (TCD) signals are directly proportional to increases in the heat activation holding time. Notably, a raw Saudi grey kaolin sample heated at a holding time of twenty-four hours resulted in the most intense TCD signal. Further, the MBOH transformations produced 3-methyl-3-buten-1-yne (MBYNE), as the main product, indicating the dehydration of MBOH due to the acidic sites of Saudi grey kaolin. The basic catalysis route was operative at the beginning of the reaction as acetone was observed only during the initial thirty-five minutes of the reaction then later dispersed entirely. Its disappearance is attributed to the high silica content of the test sample

A Flexible Optical pH Sensor Based on Polysulfone Membranes Coated with pH-Responsive Polyaniline Nanofibers

A new optical pH sensor based on polysulfone (PSU) and polyaniline (PANI) was developed. A transparent and flexible PSU membrane was employed as a support. The electrically conductive and pH-responsive PANI was deposited onto the membrane surface by in situ chemical oxidative polymerization (COP). The absorption spectra of the PANI-coated PSU membranes exhibited sensitivity to pH changes in the range of 4–12, which allowed for designing a dual wavelength pH optical sensor. The performance of the membranes was assessed by measuring their response starting from high pH and going down to low pH, and vice versa. It was found that it is necessary to precondition the sensor layers before each measurement due to the slight hysteresis observed during forward and backward pH titrations. PSU membranes with polyaniline coating thicknesses in the range of ≈100–200 nm exhibited fast response times of <4 s, which are attributed to the porous, rough and nanofibrillar morphology of the polyaniline coating. The fabricated pH sensor was characterized by a sigmoidal response (R2 = 0.997) which allows for pH determination over a wide dynamic range. All membranes were stable for a period of more than six months when stored in 1 M HCl solution. The reproducibility of the fabricated optical pH sensors was found to be <0.02 absorption units after one month storage in 1 M HCl solution. The performance of the optical pH sensor was tested and the obtained pH values were compared with the results obtained using a pH meter device

Optical and pH-Responsive Nanocomposite Film for Food Packaging Application

In this study, a biocompatible and non-toxic pH-responsive composite film was prepared for food packaging application. The films are composed from polyvinyl alcohol as the main polymeric matrix, nanoclay as a reinforcing component, and red cabbage extract as a non-toxic indicator. The prepared films showed lower water uptake values when the amount of nanoclay was increased up to 25%. It was observed that the films become brittle at high loading of nanoclay (40%). The prepared films exhibited color change in alkaline and acidic medium due to the presence of red cabbage extract, which turned pinkish in acidic medium and greenish in an alkaline environment. The prepared films were characterized by FTIR and visible spectroscopy. The maximum absorption in acidic medium was (λmax = 527 nm), while a red-shift occurred in the alkaline medium (λmax = 614 nm). Future work will focus on the crosslinking of the prepared films to improve their mechanical properties