Aqueous phase synthesis, crystal structure and antimicrobial activity of 4-(substituted phenylazo)-3-methyl-4H-isoxazol-5-one azo dyes

3-Methyl-4H-isoxazol-5-one was synthesized at room temperature by simple stirring method from ethyl acetoacetate and hydroxylamine hydrochloride in aqueous medium and coupled with diazotized substituted amine to form series of 4-(substituted phenylazo)-3-methyl-4H-isoxazol-5-ones through green chemistry. All the compounds formed were characterized by IR, 1H and 13C NMR spectroscopy, MS and elemental analysis. Crystal structure of novel 4-(4-fluorophenylazo)-3-methyl-4H-isoxazol-5-one was determined by the X-ray diffraction. Antibacterial and antifungal activity was studied against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus pyogenus and Candida albicans, Aspergillus niger, Aspergillus clavatus, respectively. All synthesized compounds were found to be active against a gram-positive bacterium Staphylococcus aureus. Two compounds showed antifungal activity against Candida albicans close to standard greseofulvin.               KEY WORDS: Azo dyes, Substituted amines, Antibacterial and antifungal activity, X-ray diffraction, Spectroscopy, Green chemistry Bull. Chem. Soc. Ethiop. 2018, 32(2), 249-257.DOI: https://dx.doi.org/10.4314/bcse.v32i2.

Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents

Antagonism of alphav beta6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an alphav beta3 antagonist lead and through simple variation in the nature and position of aryl substituent, the discovery of compounds with improved alphav beta6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery programme. Compounds 33S and 43E1 are pan alphav antagonists having ca 100 nM potency against alphav beta3, alphav beta5, alphav beta6 and alphav beta8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for alphav beta3 and alphav beta5

In silico study of CYP450 inhibitor activity of (E)-1-(3-((4-chlorophenyl) diazenyl)-4-hydroxyphenyl)ethanone

Molecular docking and single crystal study of azo dye (E)-1-(3-((4-chlorophenyl)diazenyl)-4-hydroxyphenyl)ethanone (3) is reported here. It has been synthesized by diazotization of 4-chloroaniline followed by coupling with 4-hydroxyacetophenone. Molecule is almost planar with acetyl as well as azo groups only slightly deviating from the plane of C3–C8 phenyl ring as evident by C1–C2–C3–C8 and N2–N1–C7–C6 torsion angles of –3.6(3)° and –3.9(3)°, respectively. Torsion angle N1–N2–C9–C14 between azo group and chlorophenyl ring is somewhat larger being –13.1(3)° leading to torsion angle between phenyl C3–C8 and chlorophenyl C9–C14 ring of 17.26(11)°. Intramolecular O2–H2···N2 hydrogen-bonding is observed here. Pillars along b-axis are formed due to π∙∙∙π stacking interactions of parallel molecules in head-to-head fashion with centroid-to-centroid distance of 3.8829(14) Å and ring slippage of 1.416 Å. Title compound shows good binding affinity towards six enzymes of CYP450 family. Both nitrogens of the azo bond show significant involvement in bonding interactions with proteins in case of all the six enzymes

Structural Analysis of a Peptide Fragment of Transmembrane Transporter Protein Bilitranslocase

Using a combination of genomic and post-genomic approaches is rapidly altering the number of identified human influx carriers. A transmembrane protein bilitranslocase (TCDB 2.A.65) has long attracted attention because of its function as an organic anion carrier. It has also been identified as a potential membrane transporter for cellular uptake of several drugs and due to its implication in drug uptake, it is extremely important to advance the knowledge about its structure. However, at present, only the primary structure of bilitranslocase is known. In our work, transmembrane subunits of bilitranslocase were predicted by a previously developed chemometrics model and the stability of these polypeptide chains were studied by molecular dynamics (MD) simulation. Furthermore, sodium dodecyl sulfate (SDS) micelles were used as a model of cell membrane and herein we present a high-resolution 3D structure of an 18 amino acid residues long peptide corresponding to the third transmembrane part of bilitranslocase obtained by use of multidimensional NMR spectroscopy. It has been experimentally confirmed that one of the transmembrane segments of bilitranslocase has alpha helical structure with hydrophilic amino acid residues oriented towards one side, thus capable of forming a channel in the membrane

Mediators and theories of change in psychotherapy with adolescents: A systematic review protocol

Introduction Approximately 75% of mental disorders emerge before the age of 25 years but less than half receive appropriate treatment. Little is known about the mechanisms underlying the therapeutic change of adolescents in psychotherapy. The â € European Network of Individualised Psychotherapy Treatment of Young People with Mental Disorders', funded by the European Cooperation in Science and Technology, will conduct the first systematic review to summarise the existing knowledge on mediators and theories of change in psychotherapy for adolescents. Method A systematic review will be conducted, conforming to the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement recommendations. Electronic databases (PubMed and PsycINFO) have been systematically searched on 23 February 2020, for prospective, longitudinal and case-control designs which examine mediators of change. Participants will be adolescents between 10 and 19 years of age who suffer from a mental disorder or psychological difficulties and receive an intervention that aims at preventing, ameliorating and/or treating psychological problems. Ethics and dissemination Ethical approval is not required for this systematic review as no primary data will be collected. The results will be published in a peer-reviewed journals and at conference presentations and will be shared with stakeholder groups. The whole data set will be offered to other research groups following recommendations of the open science initiative. Databases with the systematic search will be made openly available following open science initiatives

Mediators and Theories of Change in Psychotherapy for Young People With Personality Disorders: A Systematic Review Protocol

Background: Personality disorders (PDs) are a severe health issue already prevalent among adolescents and young adults. Early detection and intervention offer the opportunity to reduce disease burden and chronicity of symptoms and to enhance long-term functional outcomes. While psychological treatments for PDs have been shown to be effective for young people, the mediators and specific change mechanisms of treatment are still unclear. Aim: As part of the “European Network of Individualized Psychotherapy Treatment of Young People with Mental Disorders” (TREATme), funded by the European Cooperation in Science and Technology (COST), we will conduct a systematic review to summarize the existing knowledge on mediators of treatment outcome and theories of change in psychotherapy for young people with personality disorders. In particular, we will evaluate whether mediators appear to be common or specific to particular age groups, treatment models, or outcome domains (e.g., psychosocial functioning, life quality, and adverse treatment effects). Method: We will follow the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. Electronic databases (PubMed and PsycINFO) have been systematically searched for prospective, longitudinal, and case–control designs of psychological treatment studies, which examine mediators published in English. Participants will be young people between 10 and 30years of age who suffer from subclinical personality symptoms or have a personality disorder diagnosis and receive an intervention that aims at preventing, ameliorating, and/or treating psychological problems. Results: The results will be published in a peer-reviewed journal and at conference presentations and will be shared with relevant stakeholder groups. The data set will be made available to other research groups following recommendations of the open science initiative. Databases with the systematic search will be made openly available following open science initiatives. The review has been registered in PROSPERO (evaluation is pending, registration number ID 248959). Implications: This review will deliver a comprehensive overview on the empirical basis to contribute to the further development of psychological treatments for young people with personality disorders

Free energy of binding of coiled-coil complexes with different electrostatic environments: the influence of force field polarisation and capping

Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) simulations using the MM/GBSA method have been used to predict the free energy of interaction of these proteins. The influence of force field polarisation and capping on the predicted free energy of binding of complexes with different electrostatic environments (net charge) were investigated. Although both force field polarisation and peptide capping are important for the prediction of the absolute free energy of binding, peptide capping has the largest influence on the predicted free energy of binding. Polarisable simulations appear better suited to determine structural properties of the complexes of these proteins while non-polarisable simulations seem to give better predictions of the associated free energies of bindin