Betulin,a Newly Characterized Compound in Acacia auriculiformis Bark,Is a Multi-Target Protein Kinase Inhibitor

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from Acacia auriculiformis stem bark. Column chromatography and NMR spectroscopy were used to purify and characterize betulin from an ethyl acetate soluble fraction of acacia bark. Betulin, a known inducer of apoptosis, was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1ε (CK1ε), glycogen synthase kinase 3α/β (GSK-3 α/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6), and vascular endothelial growth factor receptor 2 kinase (VEGFR2) with activities in the micromolar range for each. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to investigate its putative use as an anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway, with activity similar to that of imatinib mesylate, a known ABL1 kinase inhibitor. The interaction of betulin and ABL1 was studied by molecular docking, revealing an interaction of the inhibitor with the ABL1 ATP binding pocket. Together, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and to potential treatments for leukemia.     

Pure phase-locking of beta/gamma oscillation contributes to the N30 frontal component of somatosensory evoked potentials

Background  

Evoked potentials have been proposed to result from phase-locking of electroencephalographic (EEG) activities within specific frequency bands. However, the respective contribution of phasic activity and phase resetting of ongoing EEG oscillation remains largely debated. We here applied the EEGlab procedure in order to quantify the contribution of electroencephalographic oscillation in the generation of the frontal N30 component of the somatosensory evoked potentials (SEP) triggered by median nerve electrical stimulation at the wrist. Power spectrum and intertrial coherence analysis were performed on EEG recordings in relation to median nerve stimulation.     

Polyhedral carbon nanoparticles at high pressures

JETP Letters - The solid-phase transformations of polyhedral nanoparticles at a pressure of 8.0 GPa and various temperatures have been investigated by X-ray diffraction, small-angle X-ray...     

Finite element computation of a turbulent flow over a two-dimensional backward-facing step

This paper is devoted to the computation of turbulent flows by a Galerkin finite element method. Effects of turbulence on the mean field are taken into account by means of a k-? turbulence model. The wall region is treated through wall laws and, more specifically, Reichardt's law. An inlet profile for ? is proposed as a numerical treatment for physically meaningless values of k and ?. Results obtained for a recirculating flow in a two-dimensional channel with a sudden expansion in width are presented and compared with experimental values.     

Identification of modified natural porphyrin isomers: 1H and 13C NMR assignments by NOESY and reverse heteronuclear shift correlation

The efficiency of two-dimensional homonuclear ¹H ¹H NOE spectroscopy in characterizing and fully assigning the ¹H NMR spectra of several isomers of meso- or ring-substituted deuteroporphyrins is demonstrated. The carbon resonances of the skeleton and the substituents were fully assigned using two-dimensional reverse heteronuclear shift correlation spectroscopy.     

Electrochemical and Spectral Characterization of Iron Corroles in High and Low Oxidation States: First Structural Characterization of an Iron(IV) Tetrapyrrole pi Cation Radical

The electrochemistry and spectroscopic properties of three iron corroles were examined in benzonitrile, dichloromethane, and pyridine containing 0.1 M tetra-n-butylammonium perchlorate or tetra-n-ethylammonium hexafluorophosphate as supporting electrolyte. The investigated compounds are represented as (OEC)Fe(IV)(C(6)H(5)), (OEC)Fe(IV)Cl, and (OEC)Fe(III)(py), where OEC is the trianion of 2,3,7,8,12,13,17,18-octaethylcorrole. Each iron(IV) corrole undergoes two one-electron reductions and two or three one-electron oxidations depending upon the solvent. Under the same solution conditions, the iron(III) corrole undergoes a single one-electron reduction and one or two one-electron oxidations. Each singly oxidized and singly reduced product was characterized by UV-vis and/or EPR spectroscopy. The data indicate a conversion of (OEC)Fe(IV)(C(6)H(5)) and (OEC)Fe(IV)Cl to their iron(III) forms upon a one-electron reduction and to iron(IV) corrole pi cation radicals upon a one-electron oxidation. The metal center in [(OEC)Fe(III)(C(6)H(5))](-) is low spin (S = (1)/(2)) as compared to electrogenerated [(OEC)Fe(III)Cl](-), which contains an intermediate-spin (S = (3)/(2)) iron(III). (OEC)Fe(III)(py) also contains an intermediate-spin-state iron(III) and, unlike previously characterized (OEC)Fe(III)(NO), is converted to an iron(IV) corrole upon oxidation rather than to an iron(III) pi cation radical. Singly oxidized [(OEC)Fe(IV)(C(6)H(5))](*)(+) is the first iron(IV) tetrapyrrole pi cation radical to be isolated and was structurally characterized as a perchlorate salt. It crystallizes in the triclinic space group P&onemacr; with a = 10.783(3) ?, b = 13.826(3) ?, c = 14.151(3) ?, alpha = 78.95(2) degrees, beta = 89.59(2) degrees, and gamma = 72.98(2) degrees at 293 K with Z = 2. Refinement of 8400 reflections and 670 parameters against F(o)(2) yields R1 = 0.0864 and wR2 = 0.2293. The complex contains a five-coordinated iron with average Fe-N bond lengths of 1.871(3) ?. The formulation of the electron distribution in this compound was confirmed by M?ssbauer, X-ray crystallographic, and magnetic susceptibility data as well as by EPR spectroscopy, which gives evidence for strong antiferromagnetic coupling between the iron(IV) center and the singly oxidized corrole macrocycle.     

Electrochemistry and Spectral Characterization of Oxidized and Reduced (TPPBr(x)())FeCl Where TPPBr(x)() Is the Dianion of beta-Brominated-Pyrrole Tetraphenylporphyrin and x Varies from 0 to 8

The electrochemistry and spectroelectrochemistry of (TPPBr(x)())FeCl (TPPBr(x)() is the dianion of beta-brominated-pyrrole tetraphenylporphyrin and x = 0-8) were examined in PhCN containing tetra-n-butylammonium perchlorate (TBAP) as supporting electrolyte. Each compound undergoes two reversible to quasireversible one-electron oxidations and either three or four reductions within the potential limits of the solvent. The two oxidations occur at the conjugated porphyrin pi ring system, and DeltaE(1/2) between these two electrode reactions increases as the molecule becomes more distorted. The overall reduction of each compound involves the stepwise electrogeneration omicronf an iron(II), iron(I), and iron(I) pi anion radical. An equilibrium between chloride-bound and chloride-free iron(II) forms of the porphyrin is observed with association of the anionic ligand being favored for compounds with x > 5. Singly reduced (TPPBr(x)())FeCl (x = 0 to x = 6) forms both mono- and bis-CO adducts in CH(2)Cl(2). Only the mono-CO adduct is observed for (TPPBr(7))FeCl, and there is no binding at all of CO to (TPPBr(8))FeCl. The nu(CO) of both the mono- and bis-adducts increases with increase in the number of Br groups, but in a nonlinear fashion which is explained in terms of two competing effects. One is the electron-withdrawing affinity of the Br substitutents and the other the nonplanarity of the macrocycle.