Novel Synthesis of some Spiro Heterocycles Derived from 3-Hydroxy-3(2-Oxocyclohexyl)-Indolin-2-One

The reaction of 3-hydroxy-3(2-oxocyclohexyl)indolin-2-one 1 with some active methylene, bidentates, phenylisocyanate, phenylisothiocyanate, carbon disulfide, benzaldehyde, ketoketene S,S-acetal, cyanoketene S,S-acetal, active halo compounds or benzylidenemalononitrile affords a series of new spiro heterocyclic systems.     

A Novel Synthesis of Heterocyclic Compounds Derived from α-Ketoketene S,S-Acetal

Novel heterocyclic compounds were prepared by the reaction of 2-acetyl-2-oxopropylidene s,s-acetal with different amino compounds namely, hydrazine hydrate, phenylhydrazine, guanidine hydrochloride, thiosemicarbazide, o-phenylenediamine, o-aminophenol or o-amino-thiophenol in different molar ratios.     

Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design,synthesis, anticonvulsant evaluation,ADMET profile and molecular docking

Molecular Diversity - In view of the anticonvulsant activity reported for phthalazine derivatives as non-competitive AMPA receptor antagonists, a new series of phthalazine-1,4-diones (2–12)...     

Urchin-like α-MnO<Subscript>2</Subscript> formed by nanoneedles for high-performance lithium batteries

MnO₂ nanoneedles (NNs) were synthesized by sol-gel assisted by a redox reaction between ascorbic acid and KMnO₄. X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), Raman, far-infrared spectroscopy, and magnetic measurements confirm the tunnel structure of the tetragonal α-MnO₂ phase. The MnO₂ NNs prepared by sol-gel at moderate temperature (T ≈ 350 °C) aggregate with an urchin-like morphology observed by scanning electron (SEM) and high-resolution transmission electron (TEM) microscopy. Electrochemical investigations show an outstanding initial specific capacity ca. 230 mAh g^?1 and 45 % capacity retention at 100th cycle was obtained for these MnO₂ nanoneedles.     

Magnetic properties of LiNi<Subscript>0.5</Subscript>Mn<Subscript>0.47</Subscript>Al<Subscript>0.03</Subscript>O<Subscript>2</Subscript> as positive electrode for Li-ion batteries

The layered LiNi_0.5Mn_0.47Al_0.03O₂ was synthesized by wet chemical method and characterized by X-ray diffraction and analysis of magnetic measurements. The powders adopted the α-NaFeO₂ structure. This substitution of Al for Mn promotes the formation of Li(Ni_0.47²⁺Ni_0.03³⁺Mn_0.47⁴⁺Al_0.03³⁺)O₂ structures and induces an increase in the average oxidation state of Ni, thereby leading to the shrinkage of the lattice unit cell. The concentration of antisite defects in which Ni²⁺ occupies the (3a) Li lattice sites in the Wyckoff notation has been estimated from the ferromagnetic Ni²⁺(3a)–Mn⁴⁺(3b) pairing observed below 140 K. The substitution of 3% Al for Mn reduces the amount of antisite defects from 7% to 6.4–6.5%. The analysis of the magnetic properties in the paramagnetic phase in the framework of the Curie–Weiss law agrees well with the combination of Ni²⁺ (S = 1), Ni³⁺ (S = 1/2) and Mn⁴⁺ (S = 3/2) spin-only values. Delithiation has been made by the use of K₂S₂O₈. According to this process, known to be softer than the electrochemical one, the nickel ions in the (3b) sites are converted into Ni⁴⁺ in the high spin configuration, while Ni²⁺(3a)–Mn⁴⁺(3b) ferromagnetic pairs remain, as the Li⁺(3b) ions linked to the Ni²⁺(3a) ions in the antisite defects are not removed. The results show that the antisite defect is surrounded by Mn⁴⁺ ions, implying the nonuniform distribution of the cations in agreement with previous NMR and neutron experiments.     

Carnosic Acid Encapsulated in Albumin Nanoparticles Induces Apoptosis in Breast and Colorectal Cancer Cells

Carnosic acid (CA) is a natural phenolic compound with several biomedical actions. This work was performed to study the use of CA-loaded polymeric nanoparticles to improve the antitumor activity of breast cancer cells (MCF-7) and colon cancer cells (Caco-2). CA was encapsulated in bovine serum albumin (BSA), chitosan (CH), and cellulose (CL) nanoparticles. The CA-loaded BSA nanoparticles (CA-BSA-NPs) revealed the most promising formula as it showed good loading capacity and the best release rate profile as the drug reached 80% after 10 h. The physicochemical characterization of the CA-BSA-NPs and empty carrier (BSA-NPs) was performed by the particle size distribution analysis, transmission electron microscopy (TEM), and zeta potential. The antitumor activity of the CA-BSA-NPs was evaluated by measuring cell viability, apoptosis rate, and gene expression of GCLC, COX-2, and BCL-2 in MCF-7 and Caco-2. The cytotoxicity assay (MTT) showed elevated antitumor activity of CA-BSA-NPs against MCF-7 and Caco-2 compared to free CA and BSA-NPs. Moreover, apoptosis test data showed an arrest of the Caco-2 cells at G₂/M (10.84%) and the MCF-7 cells at G2/M (4.73%) in the CA-BSA-NPs treatment. RT-PCR-based gene expression analysis showed an upregulation of the GCLC gene and downregulation of the BCL-2 and COX-2 genes in cells treated with CA-BSA-NPs compared to untreated cells. In conclusion, CA-BSA-NPs has been introduced as a promising formula for treating breast and colorectal cancer.     

The influence of adding marble and granite dust on the mechanical and physical properties of PP composites

Journal of Thermal Analysis and Calorimetry - The purpose of this work is to investigate the opportunity of re-using M&amp;G wastes to get novel PP composites. Recycling of marble and granite...     

Synthesis of 3,4-Biheterylthieno[2,3-b]-thiophenes. Part I: Synthesis of 3,4-Bi(1′,3′,4′-thiadiazolyl-, s-triazolyl-,1′,3′,4′-thiadiazinyl-, 1′,3′,4′-triazinyl-, thiazolyl-, 1′,3′-thiazinyl- and primidinyl)-thieno[2,3-b]thiophenes

3,4-Diamino-2,5-dicarbethoxythieno[2,3-b]thiophene ( 1 ) was allowed to react with NaNO 2 and active methylenes to afford the corresponding azo compounds 2a-c . Hydrazonyl chloride 2a was treated with carbon disulfide, phenyl isothiocyanate, benzonitrile, benzyl cyanide, malononitrile, benzalaniline, ethyl mercaptoacetate, and ethyl glycinate to give 1,3,4-thiadiazolyl-, s-triazolyl-, 1,3,4-thiadiazinyl-, 1,3,4-triazinylthieno[2,3-b]thiophenes 3-6 respectively. The reaction of 2b,c with urea, thiourea, and guanidine afforded pyrimidinyl- and thiazinylazothieno [2,3-b]thiophenes 7-10 respectively. Bithiazolylthieno[2,3-b]thiophenes 11 and 13 were synthesized by treating compound 1 with CS 2 along with halo compounds. The addition of S,S-, N,S-, and N,O-acetals to the Schiff base 14 afforded compounds 15-17 respectively.     

Synchronized stability indicating RP-LC methods for determination of metolazone with losartan potassium or spironolactone in presence of their degradation products

Abstract

Two precise and selective stability-indicating RP-LC methods have been developed and validated for simultaneous determination of metolazone in its binary mixture with losartan potassium (method 1) and spironolactone (method 2) in the presence of their degradation products. For method 1, the chromatographic separation was achieved on Kromasil C₁₈ column, the mobile phase consisted of a mixture of 0.1% ortho-phosphoric acid in acetonitrile and 0.1% ortho-phosphoric acid in water (28:72, v/v) pumped at flow rate 2?mL/min and UV detection at 235?nm. Linearity was determined over the concentration range of 2–16µg/mL for metolazone and 40–320µg/mL for losartan potassium. For method 2, chromatographic separation of metolazone and spironolactone was achieved on a Symmetry C₈ column using a mobile phase that consisted of acetonitrile, methanol, and 0.1% ortho-phosphoric in water in gradient mode pumped at a flow rate 1.5?mL/min with programed wavelength detection. Linearity was determined over the concentration range of 2–16µg/mL for metolazone and 20–160µg/mL for spironolactone. The suggested methods were proved to be highly selective, precise and accurate for simultaneous determination of the cited drugs in their combined pharmaceutical dosage form in the presence of their degradation products. The proposed methods were validated in compliance with ICH guidelines.

1. Highlights

2. Synchronized determination of metolazone and co-formulated drugs in presence of their degradation products.

3. Act as a method for screening of metolazone and co-formulated drugs in quality control laboratories.

4. Validation of suggested methods according to ICH guidelines.

5. The pathway of degradation of metolazone under different stress conditions was proposed.

     

Synthesis of Some Novel Fused Azole Derivatives

A novel synthesis of pyrazolopyrimidine derivatives was reported wherein 5-amino-1-benzoyl-3-(methylthio)-1H-pyrazole-4-carbonitrile was treated with formic acid, formamide, thioacetamide, carbon disulfide, and phenylisocyanate and phenylisothiocyanate.