Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (2³) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of −28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.     

Polymer‐Supported Sulfonic Acid‐Catalyzed Candid Synthesis and Photophysical Properties of 2H‐indazolo[2,1‐b]phthalazinetriones

Polystyrene‐supported sulfonic acid has been found to be an efficient catalyst for the one‐pot, three‐component synthesis of 2H‐indazolo[2,1‐b]phthalazinetriones in greener solvent glycerol. Use of greener solvent glycerol along with a polymer‐supported, low toxic, and inexpensive catalyst renders the method eco‐friendly. High yields, simple product isolation procedure, and fluorescent and electroluminescent natures of the products are the noteworthy aspects of this protocol.     

Sequence Selective Michael Addition for Synthesis of Indeno‐Pyridine and Indeno‐Pyran Derivatives in One‐Pot Reaction Using CuO Nanoparticles in Water

The alternate synthesis of indeno‐pyridine and indeno‐pyran derivatives have been described by an unprecedented, green, one‐pot reaction of aromatic aldehydes, malononitrile, and indane 1,3‐dione. The formation of either indeno‐pyridine or indeno‐pyran derivatives based on a precise change in the Michael addition of indane 1,3‐dione or malononitrile on Knoevenagel product during the progress of reaction has been investigated. The reaction completed up to 30 min of time using CuO nanoparticles in water at an ambient temperature renders the protocol novel and environment friendly. All the synthesized compounds have been confirmed on the basis of their spectroscopic data. The CuO nanoparticles have been prepared by coprecipitation method and characterized by SEM, PXRD spectroscopy, and UV spectroscopy.     

Microwave‐assisted Synthesis of 6‐{(5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines

An efficient and convenient synthesis of a new series of 2‐{(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)methyl}‐5‐aryl‐1,3,4‐oxadiazoles from readily available 1,2‐diaminobenzene and isatins under microwave irradiation conditions was disclosed. The 6‐{(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines were also prepared by the thermal cyclo‐condensation reaction of 2‐(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)acetohydrazides with carboxylic acids in refluxing POCl₃. The microwave‐assisted synthesis was rapid and resulted in higher yield of the products at lower operating temperature with reduced waste generation in comparison with the thermal reaction protocol.     

Production of Mycophenolic Acid by <Emphasis Type="Italic">Penicillium brevicompactum</Emphasis> Using Solid State Fermentation

Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KH₂PO₄ 8.0, MgSO4?7H₂O 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.     

Influence of high loading of cellulose nanocrystals in polyacrylonitrile composite films

Polyacrylonitrile-co-methacrylic acid (PAN-co-MAA) and cellulose nanocrystal (CNC) composite films were produced with up to 40 wt% CNC loading through the solution casting method. The rheological properties of the solution/suspensions and the structural, optical, thermal, and mechanical properties of the resulting films were investigated. The viscosity of the composite suspensions increased with higher CNC loadings and with longer aging times. PAN-co-MAA/CNC films maintained a similar level of optical transparency even with up to 40 wt% CNC loading. The glass transition temperature (Tg) increased from 92 to 118 °C, and the composites had higher thermal stability below 350 °C compared to both neat PAN-co-MAA and neat CNC. The mechanical properties also increased with higher CNC loadings, elastic modulus increased from 2.2 to 3.7 GPa, tensile strength increased from 75 to 132 MPa, and the storage modulus increased from 3.9 to 10.5 GPa. Using the Kelly and Tyson model the interfacial shear strength between the PAN-co-MAA and CNC was calculated to be 27 MPa.     

Synthesis and characterization of thermally stable poly(ether-azomethine)s derived from 1,1-bis[4-(4-benzaldehyde oxy)-3-methyl phenyl] cyclopentane

A new dialdehyde 1,1-bis[4-(4-benzaldehyde oxy)-3-methyl phenyl] cyclopentane (BBMPC) was synthesized starting from cyclopentanone and O-cresol to give 1,1-bis(4-hydroxy-3-methyl phenyl)cyclopentane (BHMPC); followed by reaction with 4-fluorobenzaldehyde in N, N-dimethyl formamide (DMF), containing anhydrous potassium carbonate. New series of poly(ether-azomethine)s were synthesized from (BBMPC) with different diamines such as 4,4′- diamino diphenyl ether (ODA); 4,4′-diaminodiphenyl methane (MDA); 4-aminophenyl sulfone (SDA); p-phenylene diamines (p-PDA), etc. in N, N’- dimethyl acetamide (DMAc) with 5 wt% LiCl by the solution polycondensation method. Inherent viscosities of these polymers were in the range 0.20 to 0.38 dL/g indicating formation of moderate molecular weights. These polymers exhibited good solubility in various polar aprotic solvents such as N-methyl-2-pyrrolidone (NMP), DMAc, DMF, etc. However some polymers showed partial solubility in DMF and DMAc. X-Ray diffraction pattern of polymers showed amorphous nature. Thermal stability was assessed by 10% weight loss temperature and the degradation temperature of the resultant polymers falls in the ranges from 444-501°C in nitrogen. The glass transition temperature was in the range of 155-205°C. The structure-property correlation among these polyazomethines were studied; in view of their potential applications as high performance polymers.     

On the explosive instability in a three‐species food chain model with modified Holling type IV functional response

In earlier literature, a version of a classical three‐species food chain model, with modified Holling type IV functional response, is proposed. Results on the global boundedness of solutions to the model system under certain parametric restrictions are derived, and chaotic dynamics is shown. We prove that in fact the model possesses explosive instability, and solutions can explode/blow up in finite time, for certain initial conditions, even under the parametric restrictions of the literature. Furthermore, we derive the Hopf bifurcation criterion, route to chaos, and Turing bifurcation in case of the spatially explicit model. Lastly, we propose, analyze, and simulate a version of the model, incorporating gestation effect, via an appropriate time delay. The delayed model is shown to possess globally bounded solutions, for any initial condition. Copyright © 2017 John Wiley & Sons, Ltd.     

Uncatalyzed four-component synthesis of pyrazolopyranopyrimidine derivatives and their antituberculosis activities

Fused pyrazolopyranopyrimidines containing both biologically active pyranopyrazole and pyranopyrimidine compounds were synthesized using a one-pot, four-component reaction of ethyl aceto acetate, hydrazine hydrate, benzaldehydes, and thiobarbituric acid without catalyst in ethanol. All target compounds obtained in very good to excellent yields over short reaction times by adapting a simple workup procedure. All the synthesized compounds exhibited good to excellent antituberculosis activities. The results shown that 4-(1H-imidazol-2-yl)-3-methyl-7-thioxo-4,6,7,8-tetrahydropyrazolo[4’,3′:5,6]pyrano[2,3-d] pyrimidin-5(1H)-one (5a) is a good antitubercular agent, as good as the standard streptomycin drug, based on minimum inhibitory concentration (MIC).     

Isolation and total synthesis of two novel metabolites from the fissurellid mollusc Scutus antipodes

There is almost no information on natural products from gastropods in the order Vetigastropoda and nothing at all for the superfamily Fissurellidae (keyhole and slit limpets), which are only partially protected from predation by their shell. Extraction of the Australian fissurellid Scutus antipodes yielded two new compounds, scutinin A [d-sorbityl hexakis(p-hydroxybenzoate)] and scutinin B [2-ethylhexane-1,3-bis(p-hydroxybenzoate)] that were identified by spectroscopic analysis and their structures confirmed by total synthesis. The compounds were found to have antimicrobial activity but no fish antifeedant activity.