Unrevealing the Potential of Sansevieria trifasciata Prain Fraction for the Treatment of Androgenetic Alopecia by Inhibiting Androgen Receptors Based on LC-MS/MS Analysis,and In-Silico Studies

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieria trifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3′, 4′-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-β-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of −7.0, −5.8, −5.2, and −6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of −66.13, −59.36, −40.39, and −40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach.     

Developing photoactive affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases

The denaturing aspect of current activity-based protein profiling strategies limits the classes of chemical probes to those which irreversibly and covalently modify their targeting enzymes. Herein, we present a complimentary, affinity-based labeling approach to profile enzymes which do not possess covalently bound substrate intermediates. Using a variety of enzymes belonging to the class of metalloproteases, the feasibility of the approach was successfully demonstrated in several proof-of-concept experiments. The design template of affinity-based probes targeting metalloproteases consists of a peptidyl hydroxamate zinc-binding group (ZBG), a fluorescent reporter tag, and a photolabile diazirine group. Photolysis of the photolabile unit in the probe effectively generates a covalent, irreversible linkage between the probe and the target enzyme, rendering the enzyme distinguishable from unlabeled proteins upon separation on a SDS-PAGE gel. A variety of labeling studies were carried out to confirm that the affinity-based approach selectively labeled metalloproteases in the presence of a large excess of other proteins and that the success of the labeling reaction depends intimately upon the catalytic activity of the enzyme. Addition of competitive inhibitors proportionally diminished the extent of enzyme labeling, making the approach useful for potential in situ screening of metalloprotease inhibitors. Using different probes with varying P(1) amino acids, we were able to generate unique "fingerprint" profiles of enzymes which may be used to determine their substrate specificities. Finally, by testing against a panel of yeast metalloproteases, we demonstrated that the affinity-based approach may be used for the large-scale profiling of metalloproteases in future proteomic experiments.     

AlCl3/PCC-SiO2-Promoted Oxidation of Azaindoles and Indoles

Abstract

A simple and efficient method is described for the oxidation of 7-azaindoles and indoles to 7-azaisatins and isatins using pyridinium chlorochromate–silica gel (PCC-SiO₂) with the aid of Lewis acid catalyst aluminium chloride (AlCl₃) in dichloroethane. Simplicity of the reaction conditions, easy workup procedure, and good yields are the key features of this protocol.     

Thermodynamics and kinetics of NaAlH4 nanocluster decomposition

Reactive nanoparticles are of great interest for applications ranging from catalysis to energy storage. However, efforts to relate cluster size to thermodynamic stability and chemical reactivity are hampered by broad pore size distributions and poorly characterized chemical environments in many microporous templates. Metal hydrides are an important example of this problem. Theoretical calculations suggest that reducing their critical dimension to the nanoscale can in some cases considerably destabilize these materials and there is clear experimental evidence for accelerated kinetics, making hydrogen storage applications more attractive in some cases. However, quantitative measurements establishing the influence of size on thermodynamics are lacking, primarily because carbon aerogels often used as supports provide inadequate control over size and pore chemistry. Here, we employ the nanoporous metal-organic framework (MOF) Cu-BTC (also known as HKUST-1) as a template to synthesize and confine the complex hydride NaAlH(4). The well-defined crystalline structure and monodisperse pore dimensions of this MOF allow detailed, quantitative probing of the thermodynamics and kinetics of H(2) desorption from 1-nm NaAlH(4) clusters (NaAlH(4)@Cu-BTC) without the ambiguity associated with amorphous templates. Hydrogen evolution rates were measured as a function of time and temperature using the Simultaneous Thermogravimetric Modulated Beam Mass Spectrometry method, in which sample mass changes are correlated with a complete analysis of evolved gases. NaAlH(4)@Cu-BTC undergoes a single-step dehydrogenation reaction in which the Na(3)AlH(6) intermediate formed during decomposition of the bulk hydride is not observed. Comparison of the thermodynamically controlled quasi-equilibrium reaction pathways in the bulk and nanoscale materials shows that the nanoclusters are slightly stabilized by confinement, having an H(2) desorption enthalpy that is 7 kJ (mol H(2))(-1) higher than the bulk material. In addition, the activation energy for desorption is only 53 kJ (mol H(2))(-1), more than 60 kJ (mol H(2))(-1) lower than the bulk. When combined with first-principles calculations of cluster thermodynamics, these data suggest that although interactions with the pore walls play a role in stabilizing these particles, size exerts the greater influence on the thermodynamics and reaction rates.     

Advanced analytical tools in proteomics

Proteomics deals with the study of proteins, their structures, localizations, posttranslational modifications, functions and interactions with other proteins. The mapping of protein structure-function holds the key to a better understanding of cellular functions under both normal and disease states, which is critical for modern drug discovery. However, the study of human proteome presents scientists with a task much more daunting than the human genome project. In fact, the estimated >100,000 different proteins expressed from 30,000 to 40,000 human genes make it extremely challenging, if not impossible with existing protein analysis techniques, to map the entire cellular functions at the translational level. Consequently, there have been rapid advances in the techniques and methods capable of large-scale proteomic studies. Among them, the recently developed high-throughput screening methods have enabled scientists to analyze proteins quickly and efficiently at an organism-wide scale. Herein, we overview some of these emerging tools for high-throughput protein analysis. In particular, we focus on recent advances in the bioassay development, which has provided sensitive and selective tools for high-throughput identification and characterizations of enzymes. Finally, the recently developed bioimaging techniques to visualize and quantify proteins in living cells are also discussed.     

Acetyltrimethylsilane: a novel reagent for the transformation of 2H-pyran-2-ones to unsymmetrical biaryls

[reaction: see text] An expeditious synthesis of unsymmetrical biaryls functionalized with electron-withdrawing or -donating substituents is described and illustrated by carbanion-induced ring transformation of 2H-pyran-2-one using acetyltrimethylsilane (ATMS) as a novel reagent in good yield. The novelty of the reaction lies in the creation of an aromatic ring from 2H-pyran-2-ones via two-carbon insertion from ATMS used as a source of carbanion.     

Characterization of C4H in the A2Π and X2Σ+ states by double resonance four-wave mixing

The B(2)Π-X(2)Σ(+) electronic spectrum of C(4)H has been studied by degenerate and double resonance four-wave mixing. The technique identifies vibrational levels in the X(2)Σ(+) ground state. Its sensitivity and unique characteristics permit detection of new levels. The A(2)Π state lying 222 cm(-1) above the X(2)Σ ground state is also observed, confirming the analysis from anion photoelectron spectroscopy but with improved accuracy. Vibrational level determination in the A(2)Π electronic manifold up to 700 cm(-1) above v = 0 is made. A Renner-Teller analysis is carried out for the two lowest bending modes v(6) and v(7) in the A(2)Π state by diagonalization of the effective Hamiltonian matrix. The Renner-Teller parameters ∈(6), ∈(7), and ∈(67), the vibrations ω(6) and ω(7) and the spin-orbit coupling constant A(so) are determined.     

Microwave-assisted rapid extracellular synthesis of stable bio-functionalized silver nanoparticles from guava (<Emphasis Type="Italic">Psidium guajava</Emphasis>) leaf extract

Our research interest centers on microwave-assisted rapid extracellular synthesis of bio-functionalized silver nanoparticles of 26 ± 5 nm from guava (Psidium guajava) leaf extract with control over dimension and composition. The reaction occurs very rapidly as the formation of spherical nanoparticles almost completed within 90 s. The probable pathway of the biosynthesis is suggested. Appearance, crystalline nature, size and shape of nanoparticles are understood by UV–vis (UV–vis spectroscopy), FTIR (fourier transform infrared spectroscopy), XRD (X-ray diffraction), FESEM (field emission scanning electron microscopy) and TEM (transmission electron microscopy) techniques. Microwave-assisted route is selected for the synthesis of silver nanoparticles to carry out the reaction fast, suppress the enzymatic action and to keep the process environmentally clean and green.     

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR–PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR–PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.     

Lattice dynamics of MgO at high pressure: theory and experiment

The longitudinal acoustic and optical phonon branches along the Gamma-X direction of MgO at 35 GPa have been determined by inelastic x-ray scattering using synchrotron radiation and a diamond-anvil cell. The experimentally observed phonon branches are in remarkable agreement with ab initio lattice dynamics results. The derived thermodynamic properties, such as the specific heat CV and the entropy S are in very good accord with values obtained from a thermodynamically assessed data set involving measured data on molar volume, heat capacity at constant pressure, bulk modulus and thermal expansion.