Synthesis of 2-Oxo amide triacylglycerol analogues and study of their inhibition effect on pancreatic and gastric lipases

A general method for the synthesis of chiral 2-oxo amide triacylglycerol analogues, from (R)- or (S)-3-aminopropane-1,2-diol, was developed. These novel inhibitors of digestive lipases are analogues of the triacylglycerol molecule, a natural substrate of lipases, and they were designed to contain the 2-oxo amide functionality in place of the scissile ester bond at the sn-1 or sn-3 position and nonhydrolysable ether bonds instead of ester bonds at the other two remaining positions. The 2-oxo amide derivatives synthesised were tested for their ability to form stable monomolecular films at the air/water interface by recording their surface pressure/molecular area compression isotherms. The inhibition of porcine pancreatic and human gastric lipases by the 2-oxo amides was studied by means of the monolayer technique with mixed films of 1,2-dicaprin and with variable proportions of each inhibitor. The alpha50 values of these triacylglycerol analogues for PPL and HGL varied between 4.4 to 7.0% and 5.6 to 15.9%, respectively. The chirality at the sn-2 position of 2-oxo amide triacylglycerol analogues affected the alpha50 value for HGL, but not for PPL.     

Synthesis of symmetrical 1,5-bis-thio-substituted anthraquinones for cytotoxicity in cultured tumor cells and lipid peroxidation

The synthesis of a series of anthraquinone moieties bearing symmetrical sulfur-linked substituents in the 1 and 5 positions is described. These compounds were evaluated for their ability to inhibit the growth of suspended rat glioma C6 cells and human hepatoma G2 cells, respectively. In addition, the redox property of the compounds was determined based on the inhibition of lipid peroxidation in model membranes. Compounds 2a and 2h in this series compared favorably and exhibited the most potent cytotoxicity (0.02, 0.05 microM) against C6 cells in the XTT colorimetric assay. As far as redox properties are concerned, all bis-thio-anthraquinones show potential lipid peroxidation in model membranes very close to that of mitoxantrone (MX), and 2a, 2d, 2e, 2i, 2j, and 2k have more potential than that of MX. The lack of cytotoxicity of compound 2i cannot be related to lipid peroxidation, but the steric and electronic properties of the side-chain substituent maybe impair effective recognition of the cleavable complex. In contrast to MX, 2a and 2h are cytotoxic in rat glioma C6 cells and do not enhance lipid peroxidation in model membranes.     

An Efficient and High‐Yield One‐Pot Synthesis of Bis(oxazoline)s

An efficient and mild one‐pot synthesis of bis(oxazoline) (BOX) ligands is developed from reactions of dicarboxy dichlorides with β‐amino alcohols in the presence of 11.0 equiv. NEt₃ followed by the addition of 3.6 equiv. methanesulfonyl chloride (MsCl). Nine different BOX ligands were prepared in excellent yields of ≥ 80%. Advantages of this improved synthesis are mild reaction conditions, short total reaction time of 9 h, and high isolated yields.     

Pretilt angle of liquid crystals and liquid-crystal alignment on microgrooved polyimide surfaces fabricated by soft embossing method

In this study, the soft embossing method is proposed to fabricate periodical microgrooved structure on polyimide surfaces. These microgrooved polyimide surfaces are assembled to form liquid-crystal cells. It is found that the director of liquid crystals uniformly aligns along the groove direction even when the groove width is as high as 3 microm. The anchoring energy of these microgrooved polyimide surfaces is higher than that of the typical rubbed surfaces. The pretilt angle of liquid crystals is adjusted by tuning the surface polarity of the polyimide alignment layer, which is identified by the advancing contact angle of water. The surface polarity of polyimide alignment layers is manipulated by simply mixing two kinds of polyimide: a more hydrophilic one and a more hydrophobic one. It is found that the pretilt angle of liquid crystals increases along with the advancing contact angle of water on the alignment layer under the condition of a fixed surface topography.     

Synergistic antitumor effect of curcumin and dinitrosyl iron complexes for against melanoma cells

The aim of this study was to examine whether combining curcumin, a chemoprevention agent, and dinitrosyl iron complexes (DNICs) would have a synergistic cytotoxic effect on mouse melanoma B16-F10 cells in vitro. Three synthesized DNICs-[PPN] [(NO)₂Fe(SCH₂CONHCH₃)₂] (NC01), [PPN] [(NO)₂Fe(SCH₂CON(CH₃)₂)₂] (NC02), and [Na][(NO)₂Fe(SCH₂CON(CH₃)₂)₂] (NC03) were tested in this study. In vitro DNA cleavage assay showed all three DNICs could cause plasmid DNA damage through releasing NO under UV irradiation. The cytotoxicity assay demonstrated these DNICs were toxic to B16-F10 cells in vitro, and the estimated values of LD₅₀ (24 h of incubation) of NC01 and NC02 were 1 μM, while the values of LD₅₀ of NC03 was 200 μM. No synergistic cytotoxicity effect was noted in the treatments of the combinations of curcumin and DNICs. On the contrary, in the presence of NC03, the toxicity of curcumin was reduced. Using UV-Visible spectroscopy and fluorescence microscopy, we found NC03 might interact with curcumin and reduce the accumulation of curcumin in cells. Further experiments using the pretreatment of curcumin for 4 h followed by the treatment of NC03 showed the synergistic cytotoxic effect, while, the pretreatment of NC03 followed by the treatment of curcumin did not have any effect. This study provides the basis for further investigation on the effects of combinations of curcumin and other NO donors.     

Tritium content as indicator of environmental character on Taiwan Island

Environmental characters have been established by tritium contents in well water, coastal seawater and reservoir water collected from various places around Taiwan island. Tritium concentrations of samples were detected by a liquid scintillation analyzer TRI-CARB-LSC 2550 TR mode, with a low level standard quench curve. After samples were concentrated by electrolysis, tritium concentration was detected in optimum conditions of LLLSA. An electrolytic enrichment technique was also developed with a eurrent density of 100 mA/cm² and 0.4–0.6% (Na₂O₂) electrolyte in concentrated samples. Data observed show a lower tritium concentration for coastal seawater than for wells in the same area. The tritium concentration ratio of well and coastal seawater on the western side of Taiwan is 4.000 and on the eastern side 5.801. Tritium content of reservoir water is related to the logarithm of effective volume capacity.     

Rapid Protein Hydrolysis by Microwave Irradiation Using Heat-Resistant Teflon-Pyrex Tubes

A rapid peptide-bond hydrolysis by means of microwave irradiation is introduced for the facile preparation of protein hydrolysates used for amino acid analysis. The optimal hydrolysis condition has been determined using several enzymes with known amino acid compositions. The effects of hydrolysis time on the recovery of various labile and hydrophobic amino acids are also exemplified in the microwave heating of standard amino acids. The method has been applied to the complete amino acid analysis with a single nonvolatile solvent of methanesulfonic acid with good recovery of tryptophan and half-cystine. It provides a radical expedition of protein and peptide hydrolysis via commercial microwave ovens and specially-designed Teflon-Pyrex tubes, circumventing the tedious procedures using vacuum-sealed pyrex lubes heating at 110°C for more than 24 h. This novel type of microwave chemistry associated with rapid peptide-bond cleavage is of great potential in the automation of the complete process of amino acid analysis starting from the preparation of protein hydrolysates.     

Blends of starch with ethylene vinyl alcohol copolymers: effect of water,glycerol, and amino acids as plasticizers

Blends of thermoplastic starch with poly(ethylene‐co‐vinyl alcohol) copolymer (EVOH) were melt extruded with water/glycerol as plasticizer and a series of amino acid additives. The biggest factor in end‐use mechanical properties proved to be the relative humidity (RH) during storage. Plasticized starch‐EVOH blends stored at 0 and 50% RH changed significantly over time, with, for example, the tensile strength (TS) of the glycerol‐plasticized blend increasing from 4.7 to 26.3 MPa over 8 weeks when maintained at 0% RH. In contrast, the TS of this same sample stored at 75% RH remained unchanged for 8 weeks. Amino acids provided relatively minor, but significant changes in mechanical properties with time. Based on TS, elongation‐to‐break, and modulus, it may be concluded that β‐alanine, sarcosine, and L ‐proline were more effective than glycerol at maintaining strong flexible blends. Increases in crystallinity and changes in morphology with time, as described by modulated DSC were correlated to these changes in mechanical properties. Published in 2007 by John Wiley & Sons, Ltd.     

Reaction of Cl with CD4 excited to the second C-D stretching overtone

The effects of vibrational excitation on the Cl+CD(4) reaction are investigated by preparing three nearly isoenergetic vibrational states: mid R:3000 at 6279.66 cm(-1), |2100> at 6534.20 cm(-1), and |1110> at 6764.24 cm(-1), where |D(1)D(2)D(3)D(4)> identifies the number of vibrational quanta in each C-D oscillator. Vibrational excitation of the perdeuteromethane is via direct infrared pumping. The reaction is initiated by photolysis of molecular chlorine at 355 nm. The nascent methyl radical product distribution is measured by 2+1 resonance-enhanced multiphoton ionization at 330 nm. The resulting CD(3) state distributions reveal a preference to remove all energy available in the most excited C-D oscillator. Although the energetics are nearly identical, the authors observe strong mode specificity in which the CD(3) state distributions markedly differ between the three Cl-atom reactions. Reaction with CD(4) prepared in the |3000> mode leads to CD(3) products populated primarily in the ground state, reaction with CD(4) prepared in the |2100> mode leads primarily to CD(3) with one quantum of stretch excitation, and reaction with CD(4) prepared in the |1110> mode leads primarily to CD(3) with one quantum of C-D stretch excitation in two oscillators. There are some minor deviations from this behavior, most notably that the Cl atom is able to abstract more energy than is available in a single C-D oscillator, as in the case of |2100>, wherein a small population of ground-state CD(3) is observed. These exceptions likely result from the mixings between different second overtone stretch combination bands. They also measure isotropic and anisotropic time-of-flight profiles of CD(3) (nu(1)=1,2) products from the Cl+CD(4) |2100> reaction, providing speed distributions, spatial anisotropies, and differential cross sections that indicate that energy introduced as vibrational energy into the system essentially remains as such throughout the course of the reaction.     

Probing stereoselective inhibition of the acyl binding site of cholesterol esterase with four diastereomers of 2'-<Emphasis Type="Italic">N</Emphasis>-α-methylbenzylcarbamyl-1, 1'-bi-2-naphthol

Background  

Recently there has been increased interest in pancreatic cholesterol esterase due to correlation between enzymatic activity in vivo and absorption of dietary cholesterol. Cholesterol esterase plays a role in digestive lipid absorption in the upper intestinal tract, though its role in cholesterol absorption in particular is controversial. Serine lipases, acetylcholinesterase, butyrylcholinesterase, and cholesterol esterase belong to a large family of proteins called the α/β-hydrolase fold, and they share the same catalytic machinery as serine proteases in that they have an active site serine residue which, with a histidine and an aspartic or glutamic acid, forms a catalytic triad. The aim of this work is to study the stereoselectivity of the acyl chain binding site of the enzyme for four diastereomers of an inhibitor.