Synthesis and Biological Evaluation of Benzo[b]furans as Inhibitors of Tubulin Polymerization and Inducers of Apoptosis

A series of benzo[b]furans was synthesized with modification at the 5‐position of the benzene ring by introducing C‐linked substituents (aryl, alkenyl, alkynyl, etc.). These compounds were evaluated for their antiproliferative activities, inhibition of tubulin polymerization, and cell‐cycle effects. Some compounds in this series displayed excellent activity in the nanomolar range against lung cancer (A549) and renal cell carcinoma (ACHN) cancer cell lines. (6‐Methoxy‐5‐((4‐methoxyphenyl)ethynyl)‐3‐methylbenzofuran‐2‐yl)(3,4,5‐trimethoxyphenyl)methanone ( 26 ) and (E)‐3‐(6‐methoxy‐3‐methyl‐2‐(1‐(3,4,5‐trimethoxyphenyl)vinyl)benzofuran‐5‐yl)prop‐2‐en‐1‐ol ( 36 ) showed significant activity in the A549 cell line, with IC₅₀ values of 0.08 and 0.06 μM , respectively. G₂/M cell‐cycle arrest and subsequent apoptosis was observed in the A549 cell line after treatment with these compounds. The most active compound in this series, 36 , also inhibited tubulin polymerization with a value similar to that of combretastatin A‐4 (1.95 and 1.86 μM , respectively). Furthermore, detailed biological studies such as Hoechst 33258 staining, DNA fragmentation and caspase‐3 assays, and western blot analyses with the pro‐apoptotic protein Bax and the anti‐apoptotic protein Bcl‐2 also suggested that these compounds induce cell death by apoptosis. Molecular docking studies indicated that compound 36 interacts and binds efficiently with the tubulin protein.     

Synthesis and Biological Evaluation of Imidazo[2,1‐b][1,3,4]thiadiazole‐Linked Oxindoles as Potent Tubulin Polymerization Inhibitors

A series of imidazo[2,1‐b][1,3,4]thiadiazole‐linked oxindoles composed of an A, B, C and D ring system were synthesized and investigated for anti‐proliferative activity in various human cancer cell lines; test compounds were variously substituted at rings C and D. Among them, compounds 7 ((E)‐5‐fluoro‐3‐((6‐p‐tolyl‐2‐(3,4,5‐trimethoxyphenyl)‐imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one), 11 ((E)‐3‐((6‐p‐tolyl‐2‐(3,4,5‐trimethoxyphenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one), and 15 ((E)‐6‐chloro‐3‐((6‐phenyl‐2‐(3,4,5‐trimethoxyphenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one) exhibited potent anti‐proliferative activity. Treatment with these three compounds resulted in accumulation of cells in G₂/M phase, inhibition of tubulin assembly, and increased cyclin‐B1 protein levels. Compound 7 displayed potent cytotoxicity, with an IC₅₀ range of 1.1–1.6 μM , and inhibited tubulin polymerization with an IC₅₀ value (0.15 μM ) lower than that of combretastatin A‐4 (1.16 μM ). Docking studies reveal that compounds 7 and 11 bind with αAsn101, βThr179, and βCys241 in the colchicine binding site of tubulin.     

Extruded aquafeeds containing distillers dried grains with solubles: effects on extrudate properties and processing behaviour

BACKGROUND: The tremendous supply and low cost of distillers dried grains with solubles (DDGS) make it an attractive feedstuff for aquaculture diets. Also, several studies have shown that DDGS can be successfully fed to various finfish. The objective of this study was to evaluate the effects of inclusion rate of DDGS (0, 250, 500 g kg^?1), feed moisture content (350, 450 g kg^?1) and die opening area (die A = 18.85 mm², die B = 3988.45 mm²) on the properties of the extrudates and on processing behaviour using a single‐screw extruder. RESULTS: Increasing the inclusion rate of DDGS resulted in extrudates with lower unit density, bulk density, expansion ratio, water solubility index and brightness (Hunter L) but higher redness (Hunter a) and yellowness (Hunter b). The increase in moisture content affected the extrudate properties in different ways: it increased bulk density, Hunter L, Hunter b and mass flow rate, whereas specific mechanical energy decreased at high moisture content. Increasing the die opening area primarily decreased expansion ratio of extrudates, power consumption and barrel temperatures but increased mass flow rate. CONCLUSION: Extrudates from all treatments exhibited high durability and floatability, and less energy was required to produce extrudates when DDGS was used compared with soybean meal‐based diets. The aquaculture industry can use this information to develop high‐quality feeds at low cost. Copyright © 2011 Society of Chemical Industry     

Fermentation characteristics and aerobic stability of wet corn distillers grains with solubles ensiled in combination with whole plant corn

BACKGROUND: Wet corn distillers grains with solubles (WDG) are prone to aerobic spoilage when stored for an extended period of time. The objective of this study was to evaluate the fermentation characteristics of ensiling WDG with whole plant corn (WPC) using the following combinations: (1) 100% WPC; (2) 75% WPC + 25% WDG; (3) 50% WPC + 50% WDG; and (4) 100% WDG. RESULTS: The initial pH was greatest for 100% WPC and lowest for 100% WDG (5.7, 4.6, 4.0, and 3.1, respectively). Concentrations of ammonia nitrogen (12.0, 26.8, 40.7, and 50.8 g kg^?1 dry matter (DM)) and Crude protein (CP) (98.7, 155.8, 206.8, and 307.9 g kg^?1 of DM) increased with increasing concentrations of WDG. Lactic acid concentration prior to ensiling was greatest for 100% WDG (9.0 g kg^?1 DM) and decreased with WPC in the silage. Acetic, propionic, and butyric acids were not present prior to ensiling. The pH of the ensiled feeds dropped below 4.0 by day 3, with no further decrease over time. Acetic acid increased from undetected amounts at day 0 to 38.8, 43.9, 43.2, and 2.2 g kg^?1 of DM at day 129 as concentration of WDG increased. Aerobic stability was enhanced with increasing WDG concentration in the silage. CONCLUSION: Fermentation, nutrient profile, and aerobic stability can be improved when ensiling wet distillers grains with whole plant corn. Copyright © 2011 Society of Chemical Industry     

A Comparison Study Between Pre-Equalization Schemes for Single and Multi Carrier Modulation Systems

In this paper, frequency domain pre-equalization (Pre-FDE) is developed for broadband cyclic prefix-code division multiple access (CP-CDMA) as a single carrier transmission scheme, and for multi carrier-CDMA (MC-CDMA) and orthogonal frequency division multiplexing (OFDM) as multi carrier transmission schemes. A comparison study is held between these schemes and the traditional equalization schemes. Experimental results show that pre-equalization improves significantly the performance of the single and multi carrier communication systems with a very low complexity at the receiver. The comparative study between MIMO pre-equalization for single carrier systems and for multi carrier systems shows that MIMO pre-equalization for single carrier systems outperforms that for multi carrier systems in terms of bit error rate (BER) performance since single carrier transmission has more frequency diversity than multi carrier transmission in the uncoded case.     

Excess Conductivity Analysis of (Cu0.5Tl0.5)-1223 Substituted by Pr and La

Series of superconducting samples of type Cu_0.5Tl_0,5 Ba₂Ca_2?y R _y Cu₃O_10??? , where R=Pr and La with 0??y??0.20, were prepared in a sealed quartz tube via a single-step solid-state reaction technique. The prepared samples were characterized by X-ray powder diffraction (XRD), scanning electron microscope (SEM), and electron dispersive X-ray (EDX). XRD studies indicated that the tetragonal structure of (Cu_0.5Tl_0.5)-1223 phase does not change by Pr or La-substitutions whereas the lattice parameters a and c do. The elemental compositions analysis, determined from EDX, indicated that both Pr and La were successfully introduced into the microstructure of (Cu_0.5Tl_0.5)-1223 phase. The electrical resistivity ??(T) was measured as a function of temperature using conventional dc four-probe technique. The fluctuation conductivity ????, above the superconducting transition temperature T _c, was analyzed as a function of temperature using Aslamazov and Larkin model. It exhibits four different fluctuation regions namely critical (cr), three-dimensional (3D), two-dimensional (2D), and short-wave (sw). The zero-temperature coherence length, effective layer thickness of the two-dimensional system and inter-layer coupling strength were estimated as a function of the substitution-content y. Furthermore, the thermodynamics critical field, lower critical magnetic field, upper critical magnetic field, critical current density and Fermi energy were calculated from the Ginzburg number. The data indicated that both Pr and La-substitutions have quite similar behaviors.     

Performance of expellers in evacuating gas pipelines—Part II: Effects of plug valve and natural gas as a drive gas

Measurements were conducted on a typical commercial 150 mm expeller mounted on stacks with and without a plug valve and driven with natural gas. Expeller performance in terms of its mass induction ratio, correlated to the system equivalent flow resistance coefficient, was found to be the same whether the expeller is driven with air or natural gas. However, in the case of expellers driven with natural gas, the drive gas flow is reduced by a ratio corresponding to the square root of its molecular weight or specific gravity ratio and not the 60% value provided by the American Gas Association (AGA) guidelines in this regard. The effects of the presence of the plug valve along the stack on the suction flow were found to be 40% of that without a plug valve only in free-access cases. In a pipeline evacuation situation, however, the effect was found to be negligible. Revision to the current AGA guidelines is therefore needed.