Pharmacological activities of synthetic human cholecystokinin-33 of which tyrosine was sulfated by arylsulfotransferase

The pharmacological activities of synthetic human CCK-33, in which a tyrosine molecule was sulfated by arylsulfotransferase, were investigated in the rat and the guinea-pig. The activities were compared with those of non-sulfated CCK-33 (CCK-33NS), CCK-8 and CCK-4. CCK-33 was about 100 fold more potent than non-sulfated CCK-33(CCK-33NS) but was about 20 fold less potent than CCK-8 in the contraction of the isolated gallbladder of the guinea-pig. In rat pancreatic secretion, intravenous CCK-33 and CCK-8 showed almost the same activity. The potency of each was about 1000 fold more than the individual potency of CCK-33NS, non-sulfated CCK-8 (CCK-8NS) and CCK4. There were no significant differences in gastric acid stimulatory activities among CCK-33, CCK-8, CCK-4, but the activities of CCK-33NS and CCK-8NS were less than those of CCK-33 and CCK-8, respectively. CCK-33 and CCK-8 produced a reduction in the intake of powder chow in doses of 10(-8) and 3 x 10(-8) mol/kg i.p., but CCK-33NS, CCK-8NS and CCK-4 did not. In conclusion, the activities of synthetic human CCK-33 are almost the same as those of CCK-8 on exocrine pancreatic secretion, gastric acid secretion and food intake, but less than CCK-8 on isolated gallbladder contraction.     

Daily doses of biologically active UV radiation retrieved from commonly available parameters

A multiple linear correlation is done between atmospheric transmissivity for four biologically active radiation daily doses (UVB, erythemal, DNA and plant damage) T, and three parameters (daily sunshine fraction σ, cosine of the daily minimum solar zenith angle μ_min and daily total ozone column Ω). T is defined as the ratio of a daily dose to its extra‐atmospheric value. The data used are spectral UV measurements (390–400 nm at 0.5 nm step) recorded along year 2000 and over 8 months of year 2001 at Briançon Station (Alps, 1300 m above sea level) that forms part of the French UV network. The coefficients obtained from year 2000 correlation permit to retrieve daily doses for year 2001 with an average error running from 3 to 9% for monthly mean values and from 2 to 4.5% for 3‐monthly mean values, depending on daily dose type. The retrieval of yearly mean value gives an error between 4 and 7.5%. Retrieving the daily dose of a given day, where σ≥ 0.2, introduces error running from 16 to 32% depending on daily dose. An attempt to retrieve the yearly mean UVB daily dose for a northern France site, from the previous coefficients, gives encouraging results.     

Polyampholyte gels of a cross-linked polyanion or polycation network into which an oppositely charged polyion was immobilized

Three polyampholyte gels (G1 to G3) composed of acrylic acid (AA), 1-vinylimidazole (VI) and N-isopropylacrylamide (NIPA) were prepared: G1 with a pre-gel solution (pH?≈?12) containing NIPA (700 mM), AA (150 mM), VI (150 mM) and N,N′-methylenebis(acrylamide) (10 mM); G2 with the same pre-gel, except for containing poly(acrylic acid) (PAA) (150 unit mM) instead of AA; and G3 with the same pre-gel, except for containing poly(1-vinylimidazole) (PVI) (150 unit mM) instead of VI. The immobilization of PAA ( $ {\overline M_{\text{w}}} = {2}0{5},000 $ ) and PVI ( $$ {\overline M_{\text{w}}} = <$> <$>35,900 $$ ) resulted in transparent G2 and G3, respectively, while G3 with another PVI ( $ {\overline M_{\text{w}}} = {193},000 $ ) was opaque. Potentiometric titrations and swelling measurements of an anionic and a cationic copolymer gel (as a control sample) suggested that each polyampholyte gel exhibits an isoelectric point (pI) at pH?≈?5.6, at which the electrostatic attraction between the carboxylate and imidazole ions leads to gel collapse. Indeed, all the ampholyte gels underwent a collapse transition at pH around the pI upon cyclic pH changes (first increased and then decreased). The pH region where gel collapse was observed, however, was broader for G2 and G3 (with immobilized polyions) than for G1 (random terpolymer gel). The swelling/deswelling characteristics of transparent and opaque G3 gels were different from each other, and also from those of G1 and G2. These results were discussed in terms of the role of hydrogen bonding of the amide with the carboxyl or imidazole groups in the collapse transition of the ampholyte gels.     

Films solidified from a lyotropic mesophase which retain the cholesteric structure

Solidified cholesteric films of α-helical poly(γ-methyl L -glutamate) and poly(γ-benzyl L -glutamate) were prepared by casting from solutions of the lyotropic cholesteric mesophase. Colored films can be prepared in this manner, so the cholesteric structure is retained with a pitch corresponding to a visible wavelength. Their iridescent colors can cover the full range of the visible spectrum, and the colors remain unchanged for years. Although the films are similar in optical properties to those of fluid cholesteric phases, the temperature dependence of the color is quite different. On stretching, the film undergoes a permanent deformation, and the iridescent color is shifted toward the blue. If t₀ is the initial film thickness and Δt is the change in thickness after stretching the film, the relative change in pitch, ?ΔP/P₀, of the cholesteric structure increases linearly with ?Δt/t₀ in the range ?Δt/t₀ > 0.10. This reduction of the pitch is attributed to a decrease in the number of pseudonematic layers in the span of one pitch, which may be interpreted in terms of delamination using an angle-ply model of the cholesteric structure.     

Factors which influence the formation of oxadiazoles from anthranilhydrazides and other benzoylhydrazines

The cyclization of o-aminobenzoylhydrazine ( 1a ) and its 5-methyl derivative 1b with four equivalents and with one equivalent of triethyl orthoacetate (TEOA) was studied. 3-Amino-2-methyl-4(3H)-quinazolinone ( 2a ), 3,4-dihydro-2-methyl-5H-1,3,4-benzotriazepin-5-one ( 3a ) and an imino ether derivative of 2a , N-[2-methyl-4-oxo-3(4H)quinazolinyl]ethanimidic acid ethyl ester ( 4a ) were obtained from the reaction of 1a with four equivalents of TEOA. These results were compared with those of Merour [1] who isolated 2a and 3a using the same conditions. When 1a was treated with one equivalent of TEOA, 2a, 3a , and a new product, 2-(5-methyl-1,3,4-oxadiazol-2-yl)benzenamine ( 5a ) were produced, and 4a was not. Similar results were obtained with the reactions of 1b with TEOA. Authentic samples of oxadiazoles 5a and b were prepared by alternate routes. Novel acid-catalyzed rearrangements of benzotriazepinones 3a and b , to mixtures of aminoquinazolinones 2a and b and oxadiazoles 5a and b , respectively, were found. The different relative amounts of aminoquinazolinones 2 and oxadiazoles 5 which were produced from these rearrangements allowed us to choose between two potential mechanisms for these interesting rearrangements. Treatment of 5-nitrobenzoylhydrazine ( 37 ) with four equivalents of TEOA gave three products which were characterized, but did not lead to benzotriazepinone formation.     

Effect of pre-flight treatment with constant magnetic field on development of Artemia eggs retrieved from Chinese Satellite "8885"

Dry winter eggs of Artemia salina were treated with a 30-60 mT inhomogeneous constant magnetic field for 113 h, and then carried by Chinese Satellite "8885" to its spaceflight for 8 days. Their early development rate and hatching ratio were observed on the 10th, 31st, 65th and 227th days after the accomplishment of the flight. Three main results were obtained as follows: (i) The treatment accelerated the development of the eggs not flown; (ii) it also enhanced the resistance of the flown eggs against unfavorable spaceflight effects (retarding early development and lowering the hatching ratio), and promoted the recovering ability of the flown eggs from the affected state; and (iii) the latent beneficial effect produced by treatment was found to be very durable, still appearing in the development of the treated eggs on the 318th day after treatment (the 227th day after the flight).     

An approach to bi-tetrahydrofurans from glucose and a correction of the literature

The condensation of glucose with acetylacetone in the presence of zinc chloride has been found to yield the tetrahydrofuranylfuran 4 in lieu of the pyranopyran 3 reported previously.     

The new ether derivative of phenylpropanoid and bioactivity was investigated from the leaves of Piper betle L.

Abstract

A new ether derivative of phenylpropanoid compound, γ-(γ′-isohydroxychavicol)-chavicol octanyl ether (K1) along with one known phenylpropanoid named allyl-pyrocatechol or hydroxychavicol (2) were isolated from Piper betle var. kali collected from Tumluk district, West Bengal India. We first report the presence of compound K1 in the genus Piper. Their structures were established on the basis of various spectroscopic analyses. Compounds K1 and 2 showed excellent antioxidant DPPH free radical scavenging activity with IC₅₀ values of 4.61 and 4.12?µg/mL compared to ascorbic acid as a standard antioxidant drug with IC₅₀ value of 3.42?µg/mL, respectively. Evaluation of in vitro cytotoxic activities of compounds K1 and 2 showed significant effects against human oral cancer cell lines (AW13516 and AW8507), human hepatoma cell lines (HEPG2 and PLC-PRF-5) and a human pancreatic cell line (MIA-PA-CA-2), compared to Doxorubicin^® as a standard cytotoxic drug with GI₅₀ values of <10 and 18.18?µg/mL.     

Automated extraction of information from the literature on chemical-CYP3A4 interactions

A text mining system is presented for automatically extracting information from the literature on chemical-CYP3A4 interactions (i.e., substrate, induction, inhibition). The system identifies chemicals and CYP3A4 forms according to a combination of name dictionaries and context features. In addition, it transforms sentences into multiple simple clauses each containing a single event and extracts information on chemical-CYP3A4 interactions using a simple but effective pattern matching method based on the order of three keywords (chemicals, CYP3A4, key verbs). Using this system, 2990 relations including 2700 identified interactions with CYP3A4 for 600 chemicals were extracted from a corpus of 2900 PubMed abstracts. In an evaluation test using 100 randomly selected abstracts, it achieved 87.4% recall and 92.3% precision for identification of the chemical name and 85.2% recall and 92.0% precision for the extraction of chemical-CYP3A4 interactions, respectively. This system will be applicable to interactions of chemicals with any functional proteins, such as enzymes and transporters, simply by changing the list of key verbs.     

A fluorous-tagged linker from which small molecules are released by ring-closing metathesis

A fluorous-tagged linker for the parallel synthesis of small- and medium-ring and macrocyclic nitrogen heterocycles using ring-closing metathesis is described. The linker was designed such that "cyclization-release" of the cyclic heterocyclic products was coupled with liberation of the active catalyst. The design of the linker was validated using a non-fluorous-tagged model. A wide range of unsaturated alcohols were used as reagents to functionalize a fluorous-tagged sulfonamide, (Z)-{N-[4-(2-(N'-3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)-4-methylsulfonamido)methylallyloxy]but-2-enyl}-2-nitrobenzenesulfonamide, using Fukuyama-Mitsunobu reactions; in each case, fluorous-solid-phase extraction (F-SPE) was used to purify the functionalized linker from the excess reagents. In general, the "cyclization-release" of cyclic products was triggered using a light-fluorous tagged derivative of the Grubbs-Hoveyda second-generation catalyst. After the metathesis step, F-SPE was used to purify released cyclic compounds from the fluorous-tagged linker and the fluorous-tagged catalyst. The scope and limitations of the approach were determined using a range of substrates which probed different aspects of the functionalization and metathesis steps. In the study as a whole, a wide range of small- and medium-ring and macrocyclic nitrogen heterocycles were prepared using polyene and polyenyne metathesis cascades.