Inhibitor design for 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme; molecular docking and determination of molecular and electronic properties of ligands by density functional theory method

Designing new inhibitors having less side effects is a need which also could reduce cholesterol levels. To fulfill this aim, we have carried out a molecular docking study toward 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. A set of designed structural derivatives of statin drugs, eight ligands which are used as HIV-1 integrase inhibitor candidates, a set of terpenoids, and ligands downloaded from Zinc15 database were docked to HMG-CoA reductase enzyme which contains atorvastatin in crystal structure. The analysis of docking studies revealed that statin derivative ligands are more appropriate for inhibition of HMG-CoA reductase. To define the contribution of the molecular properties to the binding of ligands to enzyme structure; the highest occupied molecular orbitals-lowest unoccupied molecular orbitals, hardness, electronegativity, and chemical potential properties of ligands have best score in their sets calculated by quantum mechanical tools.     

Synthesis and monoamine oxidase A/B inhibitory evaluation of new benzothiazole-thiazolylhydrazine derivatives

Abstract

In this study, a novel series of benzothiazole-thiazolylhydrazine (3a–3i) was synthesized and their structures were characterized by ¹H-NMR, ¹³C-NMR spectrometry, and mass spectroscopy. These compounds were evaluated as inhibitors of type A and type B monoamine oxidase (MAO) enzymes. The most active compound 3b (2-((2-(2-(4-(4-Nitrophenyl)thiazol-2-yl)hydrazineylidene)-2-phenylethyl)thio)benzothiazole) showed strong inhibitory activity at hMAO-A (IC₅₀ of 0.095?±?0.004?µM). Furthermore, compound 3i (2-((2-(2-(4-(2,4-dichlorophenyl)thiazol-2-yl)hydrazineylidene)-2-phenylethyl)thio)benzothiazole) showed significant inhibition profile on hMAO-A with the IC₅₀ values 0.141?±?0.006?µM.     

Poly(allylamine hydrochloride) Functionalized Multiwalled Carbon Nanotube Modified Carbon Paste Electrode as Acetylcholinesterase Biosensor Transducer

In this work, a sensitive, practical and reliable acetylthiocholine (ATCh) biosensor based on poly(allylamine hydrochloride) functionalized multiwalled carbon nanotube (PAH/MWCNT) was fabricated and used for pesticide detection. As far as we know, this is the first work that constitutes the usage of PAH and MWCNT for ATCh biosensor. The developed system was characterized by using scanning electron microscopy, electrochemical impedance spectroscopy and cyclic voltammetry. The influence of parameters such as enzyme amount and pH were examined and a linearity between 5×10^?5 M?2.0×10^?3 M for ATCh was obtained. The proposed biosensor was applied for a model pesticide, monocrotophos, detection. The analytical curve showed an excellent linearity in the monocrotophos concentration range of 1–25 pg/mL with an incubation time of 5 min. Limit of detection and limit of quantification values were calculated as 0.88 and 2.9 pg/mL, respectively. The system was also applied for detection of monocrotophos in grape, tomatoe, tap and mineralized water samples and promising recovery values were obtained.     

Mechanism of antioxidant capacity assays and the CUPRAC (cupric ion reducing antioxidant capacity) assay

We report on the application of a simple and versatile antioxidant capacity assay for dietary polyphenols, vitamin C and vitamin E utilizing the copper(II)-neocuproine (Cu(II)-Nc) reagent as the chromogenic oxidant, which we term the CUPRAC (cupric reducing antioxidant capacity) method. It involves mixing the antioxidant solution (directly or after acid hydrolysis) with solutions of CuCl₂, neocuproine, and ammonium acetate at pH 7, and measuring the absorbance at 450 nm after 30 min. Slowly reacting antioxidants required an incubation at 50 °C for 20 min for color development. The flavonoid glycosides were hydrolyzed to their corresponding aglycones by refluxing in 1.2 M HCl-containing 50% MeOH for fully exhibiting their antioxidant potencies. Certain compounds also needed incubation after acid hydrolysis for color development. The CUPRAC absorbances of mixture constituents were additive, indicating lack of chemical deviations from Beer’s law. The CUPRAC antioxidant capacities of a wide range of polyphenolics are reported in this work and compared to those found by ABTS/persulfate and Folin assays. The trolox-equivalent capacities of the antioxidants were linearly correlated (r = 0.8) to those found by ABTS but not to those of Folin. The highest antioxidant capacities in the CUPRAC method were observed for epicatechin gallate, epigallocatechin gallate, quercetin, fisetin, epigallocatechin, catechin, caffeic acid, epicatechin, gallic acid, rutin, and chlorogenic acid in this order, in accordance with theoretical expectations. The experiences of other CUPRAC users also are summarized. Correspondence: Reşat Apak, Department of Chemistry, Faculty of Engineering, Istanbul University, Avcilar, TR-34320 Istanbul, Turkey     

Characterization,slab-pair modeling and phase analysis of circular fishnet metamaterials

Planar metamaterials, which have incident to normal plane excitation unlike SRR-type structures and that are easily fabricated in multilayer form, have received great interest in recent years. In this paper, one-dimensional and polarization independent circular fishnet metamaterials and their equivalent discontinuous slab-pair modeling for tuning resonance frequencies are introduced. After the numerical and experimental demonstration of the inclusions, the standard retrieval characterization methods and the correspondent/related backward-wave propagation observation are realized in order to check the physical explanation mentioned in the paper. In addition, a detailed phase analysis is performed in order to demonstrate the application of the suggested structure as a phase compensator.     

Single production of fourth-family quarks at the LHC

We study the single production of fourth-family quarks through the process pp→Q′jX at the Large Hadron Collider (LHC). We have calculated the decay widths and branching ratios of the fourth-family quarks (b′ and t′) in the mass range 300–800 GeV. The cross sections for the signal and background processes have been calculated in a Monte Carlo framework. It is shown that the LHC can discover single t′ and b′ quarks if the CKM matrix elements |V _t′q |,|V _qb′|≳0.01.     

Théorie des processus stochastiques généraux applications aux surmartingales

Sans résuméCe nous est un très agréable devoir d'adresser ici nos plus vifs remerciements à Monsieur J. Paris qui a bien voulu, avec une bienveillance toute particulière, veiller au meilleur déroulement de ce travail, partie de notre thèse de doctorat défendue à l'Université Catholique de Louvain.Nous sommes également très reconnaissants à Monsieur P.A. Meyer, qui nous a signalé la seconde partie du théorème 12.     

Synthesis of New Spirodifuranose Derivatives by Reduction of Stable Spiro-Endoperoxides

Synthesis of three new stable spirodifuranose derivatives (3, 5, and 7), which cannot be obtained easily using ordinary synthetic methods, has been achieved by reduction of 3-O-acetyl and 3-O-methyl derivatives of (4R)-1,2-O-alkylidene-5-eno-4,7-epidioxy-5,6,8-trideoxy-α-D-threo-1,4-furano-4,7-diulo-octoses (1, 4, and 6).