Phytoestrogens

Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens

Isolierung, Strukturermittlung und Synthese von Periplanon C und Periplanon D Untersuchungen zur Darstellung der Enantiomeren der Periplanone A, B, C, und D

Available from TIB Hannover: DW 2994 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

In vitro qualitative and quantitative CT assessment of iodinated aerosol nasal deposition using a 3D-printed nasal replica.

Computed tomography can provide high-resolution details on nasal anatomy being potentially useful for the assessment of nasal spray deposition. The purpose of this technical note was to present a method based on CT imaging to assess qualitatively and quantitatively the in vitro spray deposition patterns within the sinonasal cavities of a nasal replica obtained by three-dimensional (3D) printing, using iodinated contrast agent labelled solutions with high spatial and temporal resolution. Using a third generation dual-source CT scanner in single energy mode, scans of a nasal replica were acquired following application of iodinated contrast agent labelled aerosols with an iodine concentration of 92.5 mgl/mL. Two software programmes were then utilised (Osirix MD v.9.0, Pixmeo, Geneva, Switzerland; 3mensio, Pie Medical Imaging, Bilthoven, Netherlands) to generate three-dimensional reconstructions of the scans, thus enabling the rapid detection and visualisation of administered single droplets and their voxel-by-voxel localisation. Using this approach, we achieved recovery rates between 84-98% and 89-109% (depending on the software programme) of the total applied aerosol volume

Real-time and automated monitoring of antischistosomal drug activity profiles for screening of compound libraries

Schistosomiasis is a neglected tropical disease that affects over 200 million people annually. As the antischistosomal drug pipeline is currently empty, repurposing of compound libraries has become a source for accelerating drug development, which demands the implementation of high-throughput and efficient screening strategies. Here, we present a parallelized impedance-based platform for continuous and automated viability evaluation of Schistosoma mansoni schistosomula in 128 microwells during 72 h to identify antischistosomal hits in vitro. By initially screening 57 repurposed compounds against larvae, five drugs are identified, which reduce parasite viability by more than 70%. The activity profiles of the selected drugs are then investigated via real-time dose-response monitoring, and four compounds reveal high potency and rapid action, which renders them suitable candidates for follow-up tests against adult parasites. The study shows that our device is a reliable tool for real-time drug screening analysis of libraries to identify new promising therapeutics against schistosomiasis.ISSN:2589-004

Parallelized Impedance-Based Platform for Continuous Dose-Response Characterization of Antischistosomal Drugs

Schistosomiasis is an acute and chronic disease caused by tropical parasitic worms of the genus Schistosoma , which parasitizes annually over 200 million people worldwide. Screening of antischistosomal compounds is hampered by the low throughput and potential subjectivity of the visual evaluation of the parasite phenotypes, which affects the current drug assays. Here, an impedance‐based platform, capable of assessing the viability of Schistosoma mansoni schistosomula exposed to drugs, is presented. This automated and parallelized platform enables unbiased and continuous measurements of dose–response relationships for more than 48 h. The platform performance is established by exposure of schistosomula to three test compounds, praziquantel, oxethazaine, and mefloquine, which are known to affect the larvae phenotypes. The system is thereafter used to investigate the response of schistosomula to methiothepine, an antipsychotic compound, which causes complex drug‐induced effects. Continuous monitoring of the parasites reveals transient behavioral phenotypes and allows for extracting temporal characteristics of dose–response curves, which are essential for selecting drugs that feature high activity and fast kinetics of action. These measurements demonstrate that impedance‐based detection provides a wealth of information for the in vitro characterization of candidate antischistosomals and, represents a promising tool for the identification of new lead compounds.ISSN:2366-747

“Cap-and-Catch” Purification for Enhancing the Quality of Libraries of DNA Conjugates

The potential of DNA-encoded combinatorial libraries (DECLs) as tools for hit discovery crucially relies on the availability of methods for their synthesis at acceptable purity and quality. Incomplete reactions in the presence of DNA can noticeably affect the purity of DECLs and methods to selectively remove unreacted oligonucleotide-based starting products would likely enhance the quality of DECL screening results. We describe an approach to selectively remove unreacted oligonucleotide starting products from reaction mixtures and demonstrate its applicability in the context of acylation of amino-modified DNA. Following an amide bond forming reaction, we treat unreacted amino-modified DNAs with biotinylating reagents and isolate the corresponding biotinylated oligonucleotides from the reaction mixture by affinity capture on streptavidin-coated sepharose. This approach, which yields the desired DNA-conjugate at enhanced purity, can be applied both to reactions performed in solution and to procedures in which DNA is immobilized on an anion exchange solid support

A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition

ISSN:1860-7179ISSN:1860-718

DESIGNER Extracts as Tools to Balance Estrogenic and Chemopreventive Activities of Botanicals for Women’s Health

Botanical dietary supplements contain multiple bioactive compounds that target numerous biological pathways. The lack of uniform standardization requirements is one reason that inconsistent clinical effects are reported frequently. The multifaceted biological interactions of active principles can be disentangled by a coupled pharmacological/phytochemical approach using specialized ("knock-out") extracts. This is demonstrated for hops, a botanical for menopausal symptom management. Employing targeted, adsorbent-free countercurrent separation, Humulus lupulus extracts were designed for pre- and postmenopausal women by containing various amounts of the phytoestrogen 8-prenylnaringenin (8-PN) and the chemopreventive constituent xanthohumol (XH). Analysis of their estrogenic (alkaline phosphatase), chemopreventive (NAD(P)H-quinone oxidoreductase 1 [NQO1]), and cytotoxic bioactivities revealed that the estrogenicity of hops is a function of 8-PN, whereas their NQO1 induction and cytotoxic properties depend on XH levels. Antagonization of the estrogenicity of 8-PN by elevated XH concentrations provided evidence for the interdependence of the biological effects. A designed postmenopausal hop extract was prepared to balance 8-PN and XH levels for both estrogenic and chemopreventive properties. An extract designed for premenopausal women contains reduced 8-PN levels and high XH concentrations to minimize estrogenic while retaining chemopreventive properties. This study demonstrates the feasibility of modulating the concentrations of bioactive compounds in botanical extracts for potentially improved efficacy and safety