Investigation of indirubin derivatives: a combination of 3D-QSAR,molecular docking,and ADMET towards the design of new DRAK2 inhibitors

Kinase-related apoptosis-inducing kinase 2 (DRAK2) is a serine/threonine kinase and belongs to the death-associated protein kinase DPAK family, which is responsible for induction of apoptosis in many cell types. Thus, DRAK2 is regarded as a promising target for treatment of autoimmune diseases. To investigate the binding between DRAK2 and indirubin inhibitors and design potent inhibitors, a three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking were performed. Comparative Molecular Similarity Indices Analysis (CoMSIA) was developed using 33 molecules having pIC₅₀ ranging from 8.523 to 5.000 (IC₅₀ in nM). The best CoMSIA model gave a significant coefficient of determination (R²?=?0.93), as well as a (leave-one-out cross-validation coefficient Q² of 0.81. The predictive ability of this model was evaluated by external validation using a test set of eight compounds and yielded a predicted coefficient of determination R²_test of 0.94. The contour maps could provide structural features to improve inhibitory activity. Good consistency between contour maps and molecular docking strongly suggests that the molecular modeling is reliable. Based on these satisfactory results, we designed several new DRAK2 inhibitors and their inhibitory activities were predicted using different models, which are developed on different training and test sets. Additionally, these newly designed inhibitors showed promising results in the preliminary in silico ADMET evaluations compared to the best inhibitor from the studied dataset. This study could be useful in lead identification and optimization for early drug discovery of DRAK2 inhibitors.     

Semi-empirical correlation of solid solute solubility in supercritical carbon dioxide: Comparative study and proposition of a novel density-based model

A comprehensive data set on experimental solubility of 210 solid solutes in supercritical CO₂ counting 5550 data points has been used for comparison of the correlation performance of 21 empirical models. On the basis of the comparison results a new eight-parameter density-based model has been proposed. The comparison shows that the three-parameter models are the least accurate. The results also show that models that relate the logarithm of the solubility to the logarithm of solvent density and temperature are more accurate than models that include the pressure. When comparing the overall correlating performance in terms of average absolute relative deviation the proposed model is by far the best with an average absolute relative deviation lying in the range 0.17–81.99% and an average value of 8.88%.     

Chemical composition,antioxidant and antibacterial properties of Pteranthus dichotomus from Algerian Sahara

The phytochemical study of ethyl acetate and n-butanol extracts of Pteranthus dichotomus Forssk. led to the isolation and identification of 11 compounds, including three glycolipids 1–3, one lignan 4, three flavonoids 5–7 and four phytosterols 8–11. Structures of the isolated compounds have been elucidated by analysis of 1D and 2D NMR data, and mass spectrometry EI-MS and ESI-MS and by comparison with literature data. Furthermore, the ethyl acetate and n-butanol extracts were examined for their antioxidant and antibacterial activities. The results showed that both extracts (PDAC and PDBU) had a moderate antioxidant activity (IC50 = 375.514 μg/mL and 691.333 μg/mL) respectively.     

Bis(4‐methylbenzylammonium) tetrachloridozincate: a new noncentrosymmetric structure characterized by 13C CP–MAS NMR spectroscopy

A new noncentrosymmetric organic–inorganic hybrid material, (C₈H₁₂N)₂[ZnCl₄], has been synthesized as single crystals at room temperature and characterized by X‐ray diffraction and solid‐state NMR spectroscopy. Its novel structure consists of two 4‐methylbenzylammonium cations and one [ZnCl₄]²⁻ anion connected by N—H...Cl and C—H...Cl hydrogen bonds, two of which are three‐centre interactions. The Zn^II metal centre has a slightly distorted tetrahedral coordination geometry. Results from ¹³C CP–MAS NMR spectroscopy are in good agreement with the X‐ray structure. Density functional theory calculations allow the assignment of the carbon peaks to the independent crystallographic sites.     

Total assignment of the 1H and 13C NMR spectra of benzo[f][1]benzothieno[2,3-c]quinoline by inverse-detected two-dimensional NMR techniques

The proton and carbon nmr spectra of benzo[f][1]benzothieno[2,3-c]quinoline have been totally assigned using a combination of 2D nmr methods including concerted use of HMQC (heteronuclear multiple quantum correlation) and HMBC (heteronuclear multiple bond correlation) experiments.     

Synthesis,structural elucidation,characterization and theoretical DFT study of 1‐(o‐tolyl)biguanidium chloride

The structure of the new salt 1‐(o‐tolyl)biguanidium chloride, C₉H₁₄N₅⁺·Cl^?, has been determined by single‐crystal X‐ray diffraction. The salt crystallizes in the monoclinic space group C2/c. In this structure, the chloride and biguanidium hydrophilic ions are mostly connected to each other via N—H…N and N—H…Cl hydrogen bonds to form layers parallel to the ab plane around y = and y = . The 2‐methylbenzyl groups form layers between these layers around y = 0 and y = , with the methyl group forming C—H…π interactions with the aromatic ring. Intermolecular interactions on the Hirshfeld surface were investigated in terms of contact enrichment and electrostatic energy, and confirm the role of strong hydrogen bonds along with hydrophobic interactions. A correlation between electrostatic energy and contact enrichment is found only for the strongly attractive (N—H…Cl^?) and repulsive contacts. Electrostatic energies between ions reveal that the interacting biguanidium cation pairs are repulsive and that the crystal is maintained by attractive cation…Cl^? dimers. The vibrational absorption bands were identified by IR spectroscopy.     

Resistivity–viscosity relationship in liquid–liquid critical mixtures with added ions

Precise resistivity ρ (Ω cm) and viscosity η (10⁻² P) measurements for isobutyric acid–water (IBAW) critical mixtures with added K⁺ and Cl⁻ ions have been performed in the Arrhenius temperature domain of the electrolyte. From the activation energy, the resistivity–viscosity relation reveals a fraction power character over the whole range of parameters investigated. To analyze our data we have used an exponential formula derived from the equivalent Arrhenius law: ρ/T is proportional to (η/T)^R, where R = E_ρ/E_η is the ratio between the resistivity and viscosity activation energies. In the case of the pure system (IBAW), the value of R is in vicinity of 1, but when the salt is added, the ratio R shows dependence on the (K⁺, Cl⁻) concentrations: 0.6 < R < 1. The domain of the validity of R is in conformity with the theoretical prediction. The Coulombic interaction is the origin of the deviation.     

Transport and separation of Ag(+) and Zn(2+) by donnan dialysis through a monovalent cation selective membrane

Donnan Dialysis of Ag⁺ and Zn²⁺ was investigated through a cation exchange membrane (CMS Neosepta) when a proton concentration difference was maintained between the two sides of the membrane. Developed for the production of brine from sea water, CMS Neosepta showed a higher permeability to monovalent than to bivalent cations. Several physico-chemical parameters have been determined (electrical resistance, membrane potential, sorption of electrolytes, Zn²⁺ and Ag⁺ diffusion coefficients). The flux of Ag⁺ and the diffusion potential in the membrane increase with HNO₃ concentrations. Ag⁺ and Zn²⁺ can be separated because of the preferential membrane transfer for Ag⁺.     

More on Ordinary Differential Equations Which Yield Periodic Solutions of Delay Differential Equations

We construct a Poincaré operator for the system where λ is a real parameter, x ³, x = (x₁, x₂, x₃), [formula], and ƒ is an odd C² function such that ƒ′(0) = 1, xƒ(x) > 0, for x ≠ 0. We also consider the case where ƒ is C¹. We will express F in linearized form, that is, F(x) = Ax + G(x), where A is the linearized part of F around zero and G(x) = o(|x|) near zero. Fixed points of the Poincaré operator correspond to periodic solutions of the functional differential equation

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where T is the period of x.