In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC₅₀ (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC₅₀ (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots’ crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.     

A practical comparison of MQMAS techniques

A systematic experimental evaluation of several approaches to multiple-quantum MAS NMR was performed for spin-5/2 nuclei using (27)Al NMR of the aluminosilicate andalusite and the porous aluminum phosphate AlPO(4)-14 as model. Experiments were conducted in the fields of 9.4 and 17.6T using magic-angle spinning frequencies up to 30kHz and rf-field strengths of 250 and 120kHz. Numerical SIMPSON optimizations of the NMR parameters were performed alongside the experimental evaluations. Both theory and experiment show that the optimization is most critical for the species in the sample that have the largest quadrupolar coupling constant. For 5QMAS experiments it could be confirmed that the highest available rf-field strength and rotation frequency are favorable for the efficiency of the experiments. For 3QMAS experiments of sites with moderate quadrupolar coupling constants optimum results were obtained at less stringent conditions. The comparison of a FAM II-modification and DFS gave the expected improvement by a factor of about two with respect to a rectangular pulse. No significant difference between these techniques concerning the signal-to-noise ratios was obtained. An actual improvement of the isotropic resolution by a factor of about two was obtained going from 3QMAS to 5QMAS. In addition the resolution of the spectra increases by a factor of about two going from 9.4 to 17.6T.     

Total Synthesis and Bioactivity Mapping of Geodiamolide H

The first total synthesis of the actin-stabilizing marine natural product geodiamolide H was achieved. Solid-phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring-closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F-actin target and property computation in silico, for a better understanding of structure-activity relationships (SAR). A non-natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design.     

Theoretical stability,thin film synthesis and transport properties of the Mon +1GaCn MAX phase

The phase stability of Mo_{n +1}GaC_n has been investigated using ab‐initio calculations. The results indicate stability for the Mo₂GaC phase only, with a formation enthalpy of –0.4 meV per atom. Subsequent thin film synthesis of Mo₂GaC was performed through magnetron sputtering from elemental targets onto Al₂O₃ [0001], 6H‐SiC [0001] and MgO [111] substrates within the temperature range of 500 °C and 750 °C. High structural quality films were obtained for synthesis on MgO [111] substrates at 590 ºC. Evaluation of transport properties showed a superconducting behavior with a critical temperature of approximately 7 K, reducing upon the application of an external magnetic field. The results point towards the first superconducting MAX phase in thin film form. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Energy-Resolved Ion Mobility-Mass Spectrometry—A Concept to Improve the Separation of Isomeric Carbohydrates

Recent works using ion mobility-mass spectrometry (IM-MS) have highlighted the power of this instrumental configuration to tackle one of the greatest challenges in glycomics and glycoproteomics: the existence of isobaric isomers. For a successful separation of species with identical mass but different structure via IM-MS, it is crucial to have sufficient IM resolution. In commercially available IM-MS instruments, however, this resolution is limited by the design of the instrument and usually cannot be increased at-will without extensive modifications. Here, we present a systematic approach to improve the resolving capability of IM-MS instruments using so-called energy-resolved ion mobility-mass spectrometry. The technique utilizes the fact that individual components in an isobaric mixture fragment at considerably different energies when activated in the gas phase via collision-induced dissociation (CID). As a result, certain components can be suppressed selectively at increased CID activation energy. Using a mixture of four isobaric carbohydrates, we show that each of the individual sugars can be resolved and unambiguously identified even when their drift times differ by as little as 3 %. However, the presented results also indicate that a certain difference in the gas-phase stability of the individual components is crucial for a successful separation via energy-resolved IM-MS.

D3R grand challenge 4: blind prediction of protein–ligand poses,affinity rankings,and relative binding free energies

Journal of Computer-Aided Molecular Design - The Drug Design Data Resource (D3R) aims to identify best practice methods for computer aided drug design through blinded ligand pose prediction and...     

Carbohydrate Hydrolase-Inhibitory Activity of Juice-Based Phenolic Extracts in Correlation to Their Anthocyanin/Copigment Profile

Red fruits and their juices are rich sources of polyphenols, especially anthocyanins. Some studies have shown that such polyphenols can inhibit enzymes of the carbohydrate metabolism, such as α-amylase and α-glucosidase, that indirectly regulate blood sugar levels. The presented study examined the in vitro inhibitory activity against α-amylase and α-glucosidase of various phenolic extracts prepared from direct juices, concentrates, and purees of nine different berries which differ in their anthocyanin and copigment profile. Generally, the extracts with the highest phenolic content—aronia (67.7 ± 3.2 g GAE/100 g; cyanidin 3-galactoside; chlorogenic acid), pomegranate (65.7 ± 7.9 g GAE/100 g; cyanidin 3,5-diglucoside; punicalin), and red grape (59.6 ± 2.5 g GAE/100 g; malvidin 3-glucoside; quercetin 3-glucuronide)—showed also one of the highest inhibitory activities against α-amylase (326.9 ± 75.8 μg/mL; 789.7 ± 220.9 μg/mL; 646.1 ± 81.8 μg/mL) and α-glucosidase (115.6 ± 32.5 μg/mL; 127.8 ± 20.1 μg/mL; 160.6 ± 68.4 μg/mL) and, partially, were even more potent inhibitors than acarbose (441 ± 30 μg/mL; 1439 ± 85 μg/mL). Additionally, the investigation of single anthocyanins and glycosylated flavonoids demonstrated a structure- and size-dependent inhibitory activity. In the future in vivo studies are envisaged.