Design and Synthesis of Coumarin Derivatives as Cytotoxic Agents through PI3K/AKT Signaling Pathway Inhibition in HL60 and HepG2 Cancer Cells

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC₅₀ = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC₅₀ = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.     

Thermophoresis of Cylindrical Particle Immersed in Brinkman Fluid

Colloid Journal - This paper reports an analytical study for the thermophoresis of a circular cylindrical aerosol particle embedded in a porous medium of constant porosity based on the Brinkman...     

Internal Bremsstrahlung accompanying non-unique second-forbiddenβ-decay of36CL

The inner Bremsstrahlung spectrum (I.B.) associated wih the non-unique second forbidden-transition of³⁶Cl was measured using a single channel NaI (Tl) scintillation spectrometer. After making all the necessary corrections, the experimental results were compared with the corresponding theoretical distributions due to the KUB, Lewis and Ford, Nilsson, Ford and Martin and Chang and Falkoff. Also a comparison with those calculated according to Nilsson theory after applying the shape correction factor (M. KUB) was done. The measured spectrum is found to show fairly good agreement with M. KUB theory and its found to deviate therafter from all five theories.The authors would like to thank Prof. Dr. M. El-Nadi and Prof. Dr. O.E. Badawy for their suggestions, interest and encouragement.     

Diode array detection for stability assessment and evaluation of degradation kinetics of newly introduced sacubitril in its supramolecular complex (LCZ696) with valsartan

A newly FDA-approved heart failure therapy (LCZ696, supramolecular complex of sacubitril (SAC) and valsartan (VAL), Entresto?) is analyzed with a stability indicating HPLC–DAD method. For the newly introduced drug, SAC, there is no sufficient information about its stability under various stress conditions. The proposed chromatographic method was applied to the kinetic investigation of the acidic, alkaline, and oxidative degradation of SAC with the estimation of its activation energy and half-life at room temperature by the aid of Arrhenius plots. Kinetic investigation was conducted using either different strengths of HCl, NaOH, and H₂O₂ at one selected temperature or different temperature degrees at one selected reagent strength, for the acidic, alkaline, and oxidative stress conditions. It was found that the pseudo-first-order kinetics was followed at each case. The half-lives at room temperature using 0.1?M HCl, 0.01?M NaOH, and 15% H₂O₂ were found to be 20.50, 2.76, and 51.58?hr. The chromatographic method was achieved using Zorbax Eclipse plus-C18 (4.6?×?250?mm, 5?µm) with isocratic elution of mobile phase composed of acetonitrile and 0.025?M phosphate buffer (pH3) in a ratio of 60:40 (v/v).     

Structure and swelling-release behaviour of poly(vinyl pyrrolidone) (PVP) and acrylic acid (AAc) copolymer hydrogels prepared by gamma irradiation

Copolymer network hydrogels were prepared by gamma irradiation of aqueous solutions of poly(vinyl pyrrolidone) (PVP) and acrylic acid monomer (AAc). The composition of the final hydrogels compared to the composition of the initial preparation solutions of hydrogels was determined. The chemical structure and nature of bonding was characterized by IR spectroscopy analysis, while the thermal durability of the prepared hydrogels was assessed by thermogravimetric analysis (TGA). The kinetic swelling in water and the pH-sensitivity of PVP/AAc copolymer hydrogels was studied. The drug release properties of PVP/AAc hydrogels taking methyl orange indicator as a drug model was investigated. The IR spectra indicate the formation of copolymer networks, whereas the TGA study showed that the PVP/AAc hydrogels possess higher thermal stability than pure PAAc and lower than PVP hydrogels. The kinetic swelling in water showed that all the hydrogels reached equilibrium after 24 h and that the degree of swelling increases with increasing the ratio of AAc in the initial feeding solutions. It was found that the degree of swelling of PVP/AAc hydrogels increases greatly within the pH range 4-7 depending on composition.     

Paramagnetic charge-transfer guest–host coordination polymers. Thiophene compounds encapsulated within the channels of the three-dimensional coordination polymers [(R3Sn)3Fe(CN)6] n,R = Me,n-Bu or Ph

Various thiophene compounds have been shown to be encapsulated and partly oxidized within the channels of the three-dimensional (3D) host coordination polymers [(R₃Sn)₃Fe(CN)₆] _n (R = Me, n-Bu or Ph) to give guest–host encapsulated systems. The structure and physical properties of these systems were studied by X-ray powder diffraction, i.r., u.v.–vis., e.p.r. spectra and magnetic measurements. Thiophene compounds do not polymerize within the channels of the host, but rather give paramagnetic charge-transfer guest–host systems.     

Antibacterial,DFT and molecular docking studies of Rh(III) complexes of Coumarinyl‐Thiosemicarbazone nuclei based ligands

Coumarinyl thiosemicarbazone derivatives (1E)‐1‐(1‐(2‐oxo‐2H‐chromen‐3‐yl)ethylidene)thiosemicarbazide (OCET), (1E)‐1‐(1‐(6‐bromo‐2‐ oxo‐2H‐chromen‐3‐yl)ethylidene)thiosemicarbazide (BOCET) and 1‐(1‐(3‐oxo‐3H‐benzo[f]chromen‐2‐yl)ethylidene)thiosemicarbazide (NOCET) and their Rh(III) complexes were synthesized, the characterization was carried out by elemental analysis, IR, UV–Visible, mass, magnetic measurement and molar conductance techniques. Data interpretation of the Rh(III) complexes indicates that the ligands of coumarinyl thiosemicarbazone derivatives were formed in stoichiometric ratios as 1:2 (metal: ligand). The studied ligands act as a bidentate ligand by using both azomethine nitrogen and thiol sulphur as monoanion center of donation. The theoretical conformational structure analyses were performed using density functional theory for ligands and complexes at B3LYP functional with 6‐31G(++)d,p basis set for ligands and LANL2DZ basis set for complexes. The charge distribution within the ligands and its Rh(III) complexes was calculated using Mulliken population analysis of (MPA) and natural population analysis (NPA). The antibacterial activity of the prepared compounds was tested against some types of Gram positive and negative bacteria. Molecular docking investigation proved that, the ligands and complexes had interesting interactions with active site amino acids of ribosyltransferase (code: 3GEY).