Surveying FDA-approved drugs as new potential inhibitors of N-cadherin protein: a virtual screening approach

Since N-cadherin protein plays a remarkable role in cancer metastasis and tumor growth and progression, finding new effective inhibitors of this protein can be of high importance in cancer treatment. Nevertheless, few molecules have been introduced to inhibit N-cadherin protein to date. In this work, in order to find and present potent inhibitors, 3358 FDA-approved small molecules were docked against N-cadherin protein. All complexes with binding energy ??9 to ??8 kcal/mol were selected for protein-ligand interaction analysis. In the following, Tanimoto coefficient (T_c) was calculated for those molecules that established appropriate interactions with N-cadherin in order to compute the similarity score between them. Afterwards, molecular dynamics simulation and free energy calculations were done to estimate the stability and ability of the chosen ligands in complex with the target protein. Finally, seven small molecules among 3358 FDA-approved were suggested as potential inhibitors of N-cadherin protein.

     

‘Click Synthesis’ of 1H‐1,2,3‐Triazolyl‐Based Oxiconazole (=(1Z)‐1‐(2,4‐Dichlorophenyl)‐2‐(1H‐imidazol‐1‐yl)ethanone O‐[(2,4‐Dichlorophenyl)methyl]oxime) Analogs

The ‘click synthesis’ of some oxiconazole analogs 5a – 5v having 1H‐1,2,3‐triazolyl residues by Huisgen cycloaddition was achieved in four steps (Scheme 1). Oximation of phenacyl chloride ( 1 ) followed by azidation of 2‐chloro‐1‐phenylethanone oxime ( 2 ) provided azido ketoxime 3 . The CuI‐catalyzed Huisgen cycloaddition of 3 with terminal alkynes gave the 4‐substituted (at the triazole) 2‐(1H‐1,2,3‐triazol‐1‐yl)‐1‐phenylethanone oximes 4a – 4i . The O‐alkylation of 4a – 4i with various alkyl halides resulted in the formation of the target molecules 5a – 5v in good yields.     

Copper-doped silica cuprous sulfate (CDSCS) as a highly efficient and new heterogeneous nano catalyst for [3+2] Huisgen cycloaddition

The synthesis and characterization of copper-doped silica cuprous sulfate (CDSCS) as a new and efficient heterogeneous nano catalyst are described. CDSCS has been fully characterized by different microscopic, spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic forced microscopy (AFM), X-ray diffraction (XRD), inductively coupled plasma (ICP) analysis, thermogravimetric analysis (TGA) and FT-IR. CDSCS is proved to be a useful heterogeneous nano catalyst in Cu(I)-catalyzed ‘Click’ cycloaddition of organic azides with terminal alkynes. CDSCS catalyzes the 1,3-dipolar cycloaddition reactions of β-azido alcohols and alkynes at room temperature, in THF/H₂O (1:1, v/v) solution. Using CDSCS, 1,4-disubstituted 1,2,3-triazole adducts are mainly obtained, in good to excellent yields and in short reaction times. These compounds have featural resemblance to β-adrenoceptor blocking agents. CDSCS was approved as a chemically and thermally stable nano catalyst that can be reused for many consecutive trials without a significant decline in its reactivity.     

Adaptive fuzzy sliding mode control scheme for uncertain systems

Most physical systems inherently contain nonlinearities which are commonly unknown to the system designer. Therefore, in modeling and analysis of such dynamic systems, one needs to handle unknown nonlinearities and/or uncertain parameters. This paper proposes a new adaptive tracking fuzzy sliding mode controller for a class of nonlinear systems in the presence of uncertainties and external disturbances. The main contribution of the proposed method is that the structure of the controlled system is partially unknown and does not require the bounds of uncertainty and disturbance of the system to be known; meanwhile, the chattering phenomenon that frequently appears in the conventional variable structure systems is also eliminated without deteriorating the system robustness. The performance of the proposed approach is evaluated for two well-known benchmark problems. The simulation results illustrate the effectiveness of our proposed controller.     

Systematically engineered electrospun conduit based on PGA/collagen/bioglass nanocomposites: The evaluation of morphological,mechanical, and bio‐properties

Peripheral nerve injury can considerably affect the daily life of affected people through reduced function and permanent deformation of the nerve. One of the conventional treatments used for the management of the disease is the application of autograft, which is recognized as a golden standard method; however, the process of gaining access to autograft has posed a significant challenge to its use. Nerve guidance channels (conduits), which are made in different methods, can act as an alternative therapy for patients that have undergone nerve injury; but, achieving these conduits has always been a major dilemma to be applied for patients with nerve injury. In this study, a novel conduit based on polymer blend nanocomposites of polyglycolic acid (PGA), collagen, and nanobioglass (NBG) were prepared by electrospinning technique and then compared with PGA/collagen and PGA conduits that were made in previous studies. Additionally, their various properties were characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), contact angle, dynamic mechanical thermal analysis (DMTA), tensile strength, Fourier‐transform infrared (FTIR), and the porosity and degradation. The results showed that the mechanical, chemical, biocompatibility, and biodegradability properties of PGA/collagen/NBG conduits were more favorable in comparison with other materials. According to 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining technique, nanofibrous electrospun PGA/collagen/NBG conduits are more suitable for cell adhesion and proliferation in comparison with either PGA or PGA/collagen conduits and can have potential for nerve regeneration.     

Crystal structure and physical properties of a new CuTi2S4 modification in comparison to the thiospinel

A new modification of CuTi(2)S(4) was prepared from the elements at 425 degrees C. It crystallizes in the rhombohedral space group Rm, with lattice parameters of a = 7.0242(4) A, c = 34.834(4) A, and V = 1488.4(2) A(3) (Z = 12). Two topologically different interlayer regions exist between the close-packed S layers that alternate along the c axis: one comprises both Cu (in tetrahedral voids) and Ti atoms (in octahedral voids), and the second exclusively Ti atoms (again in octahedral voids). In contrast to the known modification, the spinel, Cu-Ti interactions of 2.88 A occur that have bonding character according to the electronic structure calculations. Both CuTi(2)S(4) modifications are metallic Pauli paramagnets due to Ti d contributions. The Pauli susceptibility of the Rm form is larger than that of the thiospinel in quantitative agreement with the LMTO-ASA band structure calculations. The irreversible transformation to the spinel takes place at temperatures above 450 degrees C.     

Speciation analysis of mercury in water samples by cold vapor atomic absorption spectrometry after preconcentration with dithizone immobilized on microcrystalline naphthalene

Trace amounts of inorganic mercury (Hg²⁺) and methylmercury cations (MeHg²⁺) were adsorbed quantitatively from acidic aqueous solution onto a column packed with immobilized dithizone on microcrystalline naphthalene. The trapped mercury was eluted with 10 ml of 7 mol L^–1 hydrochloric acid solution. The Hg²⁺ was then directly reduced with tin (II) chloride, and volatilized mercury was determined by cold vapor atomic absorption spectrometry (CVAAS). Total mercury (Hgt) was determined after decomposition of MeHg⁺ into Hg²⁺. Hg²⁺ and MeHg⁺ cations were completely recovered from the water with a preconcentration factor of 200. The relative standard deviation obtained for eight replicate determinations at a concentration of 0.3 g L^–1 was 1.8%. The procedure was applied to analysis of water samples, and the accuracy was assessed via recovery experiment.     

Preparation of protein gradients through the controlled deposition of protein-nanoparticle conjugates onto functionalized surfaces

This paper describes a simple method for the preparation and characterization of protein density gradients on solid supports. The method employs colloidal metal nanoparticles as protein carriers and optical tags and is capable of forming linear, exponential, 1D, 2D, and multiprotein gradients of varying slope without expensive or sophisticated surface patterning techniques. Surfaces patterned with proteins using the procedures described within are shown to support cell growth and are thus suitable for studies of protein-cell interactions.     

‘Click Synthesis’ of Some Novel Benzimidazol Oxime Ethers Containing Heterocycle Residues as Potential ß‐Adrenergic Blocking Agents

The ‘click synthesis’ of some novel O‐substituted oximes, 5a – 5j , which contain heterocycle residues, as new analogs of ß‐adrenoceptor antagonists is described (Scheme 1). The synthesis of these compounds was achieved in four steps. The formation of (E)‐2‐(1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylethanone oxime, followed by their reaction with 2‐(chloromethyl)oxirane, afforded mixture of oil compounds 3 and 4 , which by a subsequent tetra‐n‐butylammonium bromide (TBAB)‐catalyzed reaction with N H heterocycle compounds (Scheme 1), led to the target compounds 5a – 5j in good yields.