Sarcorucinine-D Inhibits Cholinesterases and Calcium Channels: Molecular Dynamics Simulation and In Vitro Mechanistic Investigations

Acetylcholinesterase (AChE) inhibitors and calcium channel blockers are considered effective therapies for Alzheimer’s disease. AChE plays an essential role in the nervous system by catalyzing the hydrolysis of the neurotransmitter acetylcholine. In this study, the inhibition of the enzyme AChE by Sarcorucinine-D, a pregnane type steroidal alkaloid, was investigated with experimental enzyme kinetics and molecular dynamics (MD) simulation techniques. Kinetics studies showed that Sarcorucinine-D inhibits two cholinesterases—AChE and butyrylcholinesterase (BChE)—noncompetitively, with K_i values of 103.3 and 4.66 µM, respectively. In silico ligand-protein docking and MD simulation studies conducted on AChE predicted that Sarcorucinine-D interacted via hydrophobic interactions and hydrogen bonds with the residues of the active-site gorge of AChE. Sarcorucinine-D was able to relax contractility concentration-dependently in the intestinal smooth muscles of jejunum obtained from rabbits. Not only was the spontaneous spasmogenicity inhibited, but it also suppressed K⁺-mediated spasmogenicity, indicating an effect via the inhibition of voltage-dependent Ca²⁺ channels. Sarcorucinine-D could be considered a potential lead molecule based on its properties as a noncompetitive AChE inhibitor and a Ca²⁺ channel blocker.     

Simple Stereoselective HPLC Method for Studying the Isomerisation of Cefditoren Pivoxil and Its Isomeric Purity in Pharmaceuticals

A new rapid, simple and stereoselective HPLC method for studying the isomerisation of cefditoren pivoxil in bulk and its isomeric purity in dosage form was developed and validated. This kind of isomerisation could form due to the effect of temperature on analyte during the manufacturing process or improper storage of pharmaceutical formulations. The separation between cefditoren pivoxil and cefditoren ∆3 isomer was obtained with resolution not less than 2.00 in the presence of methanol and phosphate buffer at pH 5.20 (70:30, v:v) onto Luna C18 stationary phase within 15 min analysis time. Under the validated stereoselective HPLC conditions, isomeric purity of cefditoren pivoxil was successfully determined in tablets with inter and intra-days relative standard deviation ≤4.6 %.

     

Interactive effects of local smoothing window size and fundamental frequency on shimmer calculation

Slow amplitude modulation of human voice was approximated by a sinusoidal wave. The theoretical effects of smoothing window size, F₀, and modulation frequency on window amplitude average as well as calculated shimmer were mathematically derived. Subsequently, the theoretical predictions were tested using idealized and real voice signals from normal speakers. The theoretical and experimental results suggest that shimmer (when calculated using a smoothing window) is a function of window duration and modulation frequency. Window duration when defined as a constant number of pitch periods varies from speaker to speaker depending on their F₀. It may not be desirable to use local smoothing windows with a constant number of cycles for shimmer computation, especially if voices with known low-frequency amplitude modulations but notably different fundamental frequencies are compared.     

Voltammetric determination of hydroxylamine in water samples using a 1-benzyl-4-ferrocenyl-1H-[1,2,3]-triazole/carbon nanotube-modified glassy carbon electrode

A modified glassy carbon electrode has been constructed using a 1-benzyl-4-ferrocenyl-1H-[1,2,3]-triazole along with multiwalled carbon nanotubes. The electrochemical behaviour of modified electrode has been investigated by cyclic voltammetry. Electrocatalytic activity of the modified electrode was investigated for the oxidation of hydroxylamine in 0.1 M phosphate-buffered solution of pH 8. The modified electrode showed electrocatalytic response to the oxidation of hydroxylamine at the potential of 330 mV. The linear range and detection limit for the detection of hydroxylamine in the optimum condition were found to be 4.0?×?10^?7 to 6.75?×?10^?4 M and 28.0?±?1.0 nM, respectively. Finally, the method was employed for the determination of hydroxylamine in water samples.     

Effect of the External Mirror Feedback Strength in the Dynamics and Spectrum of the Injected Semiconductor Lasers

We analytically investigate the effect of an external mirror on the stability of an injected semiconductor laser, the latter treated as injected damped oscillators. In the studied configuration, the injected semiconductor laser with an external mirror is under the influence of a chaotic oscillating optical signal that is generated by a similar semiconductor master laser. We derive our results in terms of the damping rate and resonance frequency. We show that the external mirror can eliminate the unstable modes of the injected laser at low frequencies. Furthermore, the mirror can enhance the damping of the oscillation modes of the injected semiconductor laser; consequently, the driven response of the injected laser may have a broad spectrum, even wider than that of the chaotic driving signal. We also show results for the bandwidths of the injection amplitude and phase increment as functions of the injection rate and feedback strength of the external mirror. In addition, we use bifurcation and time-series curves to describe the dynamical behavior of the injected laser. We identify the feedback strength of injected laser, relative to that of the master laser, which induces synchronization between the injected-laser oscillation modes and the master laser.     

Biopolymer electrolytes based on carboxymethyl ҡ-carrageenan and imidazolium ionic liquid

Novel biopolymer electrolytes based on carboxymethyl kappa-carrageenan (CM?-carrageenan) and ionic liquid 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) have been successfully developed. Strong coordination and hydrogen bonding interaction of [Bmim]Cl with the biopolymer were detected by Fourier transform infrared (FTIR) spectroscopy. The efficient function of [Bmim]Cl as the charge carrier in the system was reflected by electrochemical impedance spectroscopy (EIS) where the highest ionic conductivity (σ) of (5.76 ± 0.20) × 10^?3 S cm^?1 was achieved at ambient temperature (298 K) upon 30 wt.% of [Bmim]Cl inclusion. X-ray diffraction (XRD) analysis confirmed that the addition of ionic liquid did not alter the prominent amorphous phase of CM?-carrageenan. Analysis of scanning electron microscopy (SEM) proved the strong interaction of [Bmim]Cl with the biopolymer matrix. The highest conducting biopolymer electrolyte showed an electrochemical stability up to 3.0 V, whereas the transference number measurement revealed that ions are the major elements that contribute to the conductivity with 0.970 ion transference number.