Design,Cytotoxicity and Antiproliferative Activity of 4-Amino-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylates against MFC-7 and MDA-MB-231 Breast Cancer Cell Lines

Novel 4-amino-thieno[2,3-d]pyrimidine-6-carboxylates substituted at the second position were prepared by cyclocondensation of 2-amino-3-cyano-thiophene and aryl nitriles in an acidic medium. The design of the target compounds was based on structural optimization. The derivatives thus obtained were tested in vitro against human and mouse cell lines. The examination of the compound effects on BLAB 3T3 and MFC-10A cells showed that they are safe, making them suitable for subsequent experiments to establish their antitumor activity. The photoirritancy factor of the compounds was calculated. Using the MTT test, the antiproliferative activity to MCF-10A, MCF-7 and MDA-MB-231 cell lines was estimated. The best antiproliferative effect in respect to the MCF-7 cell line revealed compound 2 with IC₅₀ 4.3 ± 0.11 µg/mL (0.013 µM). The highest selective index with respect to MCF-7 cells was shown by compound 3 (SI = 19.3), and to MDA-MB-231 cells by compound 2 (SI = 3.7). Based on energy analysis, the most stable conformers were selected and optimized by means of density functional theory (DFT). Ligand efficiency, ligand lipophilicity efficiency and the physicochemical parameters of the target 4-amino-thienopyrimidines were determined. The data obtained indicated that the lead compound among the tested substances is compound 2.     

Influence of the discharge gas on the emission and thermal characteristics of laser-induced microplasmas

Summary An investigation has been made of the influence of argon, oxygen, and argon/oxygen blends in various ratios as the protective gas medium, on the intensities of the spectral lines, the amount of substance evaporated, and the excitation temperatures in the evaporation of an aluminium sample with the aid of laser irradiation and subsidiary excitation of the microplasma obtained. Maximum intensifying effect was observed when a pure argon medium was used. The gas medium does not influence the amount of substance evaporated from the sample. Within the experimental error of the twoline method used, the excitation temperatures do not appear to be influenced by the type of gas blend. An auxiliary voltage device was added to the laser equipment, which allows evaporation of the substance in an atmosphere of inert gas and in minute absolute amounts, with high energy in the discharge gap. This new approach improves the limits of detection.

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Zusammenfassung Der Einfluß der Schutzgasatmosphäre aus Argon, Sauerstoff oder Argon/Sauerstoff-Mischung in verschiedenen prozentualen Verhältnissen auf die Intensitäten der Spektrallinien, die Menge der verdampften Substanz und die Anregungstemperaturen wurde bei der Verdampfung einer Aluminiumprobe mit Hilfe von Laserstrahlung und mit Nebenanregung des Mikroplasmas untersucht. Ein maximaler Verstärkungseffekt wurde in reinem Argon beobachtet. Das Gasmedium übt keinen Einfluß auf die Menge der verdampften Probensubstanz aus. Im Rahmen der Fehler und der Genauigkeit der angewandten Zweilinienmethode wurden die Anregungstemperaturen von der Art der Gasmischung nicht beeinflußt. Die Laserausrüstung war mit einer Vorrichtung für Hilfsspannung ausgestattet, welche die Verdampfung und Anregung der Probensubstanz in einer Inertgasatmosphäre und in minimalen absoluten Mengen unter Hochenergiebildung in der Entladungsstrecke ermöglichte. Damit konnten die Nachweisgrenzen der Mikroelemente erweitert werden.

     

Experimental and Theoretical Study on the Homodimerization Mechanism of 3-Acetylcoumarin

In the present study, the reaction conditions for homodimerization process of 3-acetylcoumarin were achieved under sonication using combination of zinc and metallic salt (ZnCl₂ or Zn(OAc)₂). Appropriate frequency and sound amplitude have been identified as significant variables for the initiation of the reaction. On the base of first principal calculations and experimental results, the mechanism of the reaction was investigated. The relative stability of the possible intermediates has been compared, including evaluation on the ionic and radical reaction pathways for the dimerization process. Theoretical results suggested that the radical mechanism is more favorable. The C-C bond formation between the calculated radical intermediates occurs spontaneously (∆G = −214 kJ/mol for ZnCl₂, −163 kJ/mol in the case of Zn(OAc)₂), which proves the possibility for the homodimerization of 3-acetylcoumarin via formation of radical species. Both experimental and theoretical data clarified the activation role of the solvent on the reactivity of the Zn-salt. The formation of complexes of solvent molecules with Zn-atom from the ZnCl₂ reduces the energy barrier for the dissociation of Zn-Cl bond and facilitate the formation of the dimeric product.     

NiH3IO6 · 6H2O — Kristallstruktur und Schwingungsspektren

NiH₃IO₆ · 6 H₂O — Crystal Structures and Vibrational Spectra The crystal structure of NiH₃IO₆ · 6 H₂O has been determined by X-ray single-crystal diffraction (Pc, Z = 2, a = 516.74(9), b = 981.5(2), c = 1052.5(2) pm, β = 116.496(8)°) on the basis of 4169 unique reflections (R = 1.96%). The structure is built up of distorted Ni(H₂O)₆²⁺ and H₃IO₆^2? octahedra linked by hydrogen bonding. IR and Raman spectra of both the title compound and isostructural MgH₃IO₆ · 6 H₂O as well as of deuterated specimens are given. There are up to 14 different OH(OD) modes in the spectra of isotopically dilute samples due to the 15 different hydrogen positions of the structure. The internal modes of the meridional H₃IO₆^2? ions (pseudo C_2v symmetry) are discussed with respect to that double T-shaped entity, which gives rise to only two instead of 3I? O, I? O(H), and OH stretches in the IR and Raman spectra, i.e. the same as for facial (C_3v) structured ions.     

Effect of the Structure of 1- and 3-Methylpyrimidin-4-ones on the Rate of Nucleophilic Substitution of the 2-Methylsylfanyl Group

Rate constants for substitution of the 2-methylsulfanyl group in 1- and 3-methyl-2-methylsulfanyl-pyrimidin-4-ones and their 5-fluoro analogs were measured in the reaction with butylamine, alkaline hydrolysis, and methanolysis. The rate of substitution in 1-methyl isomers having a zwitterionic structure is greater by a factor of ~2 than the rate of substitution in 3-methyl isomers with conjugated double bonds in the ring. The presence of a fluorine atom in position 5 accelerates nucleophilic substitution in 1-methyl isomers, while 5-fluoro-3-methyl-2-methylsulfanylpyrimidin-4-ones react at a lower rate than their 5-unsubstituted analogs. According to the NMR data, the reactions involve formation of a tetrahedral intermediate. Anchimeric effect of the methyl group on N¹ hampersattack by basic reagent on the C⁶atom.     

Crystal structure of a new small-pore zirconosilicate Na2ZrSi2O7·H2O and its relation to stoichiometrically and topologically similar compounds

The small-pore zirconosilicate Na₂ZrSi₂O₇·H₂O crystallizes in monoclinic system with space group C2/c, a = 5.4715(4); b = 9.4111(6); c = 13.0969(8) Å, β = 92.851(7)°. Its framework consists of layers built of ZrO₆ octahedra and SiO₄ tetrahedra and forming condensed [Si₂O₇] pyrogroups by connection. The sodium ions and water molecules are placed in channels set up between the layers. The stoichiometric and structural similarities of the studied phase with anhydrous compounds having general chemical formula A₂₍₃₎MT₂O₇ (A = Na,K; M = Zr,Lu,Sc; T = Si,Ge) are discussed. The topological relationship of their structures is interpreted in the light of spatial combination of silicon and zirconium polyhedra as basic building units into larger composite building units and their three-dimensional arrangement.     

The uniform convexity of the Edmunds-Triebel logarithmic spaces

We show how uniform convexity can be preserved in the logarithmic spaces A_θ(logA)_b,p. Estimates are given for the moduli of convexity of A_θ(logA)_b,p in terms of the moduli of A₀ and A₁, when one or both of them are uniformly convex.     

Influence of nutrient medium composition on in vitro growth, polyphenolic content and antioxidant activity of Alchemilla mollis

Alchemilla mollis (Buser) Rothm. (Rosaceae) is a high-mountain medicinal plant growing in the Balkan Peninsula, with only one population in Bulgaria. Alchemilla plants (Lady's mantle) are commonly used in traditional medicine for treatment of many gynecological diseases. The commercial drugs "Herba Alchemillae" induce a rapid regeneration of skin epithelium and have styptic and anti-inflammatory actions. Because of the high content of phenolic compounds (tannins and flavonoids) and the ecological plasticity of the species, field cultivation or in vitro biomass production of A. mollis are possible alternatives to its collection from nature. Four MS based nutrient media differing in the concentration of the minerals and supplemented with alpha-naphthaleneacetic acid (NAA) and benzylaminopurine (BAP) were tested in order to examine their influence on the shoot multiplication effectiveness and the antioxidant activity of A. mollis, and also the possible relation between these parameters under the conditions of in vitro culture. The cultures grown for two months on these media differed significantly in their multiplication rates (p < 0.001), as well as in their morphological features--height, leaf color and root development. Methanol extracts of in vitro cultivated and ex vitro adapted and acclimated on Vitosha Mt. (1500 m a. s. l.) plants were analyzed for tannin and flavonoid content and for free radical scavenging activity. The contents of flavonoids and tannins in the in vitro cultures of A. mollis cultivated on the four tested media differed significantly (p < 0.05). The highest flavonoid content was found in the shoots cultivated on the control MS medium, as well as in the ex vitro adapted plants. The antioxidant activity of the in vitro cultures correlated positively with the concentrations of the PGRs in the respective media, and the ex vitro adapted plants had the highest antioxidant activity (IC50 13.1 +/- 1.9 microg/mL) commensurable with that of the commercial antioxidant butylated hydroxytoluene (BHT) used as a positive control, with an IC50 of 12.65 microg/mL.     

Catalytic performance of Ni-Al layered double hydroxides in CO purification processes

Ni-Al layered double hydroxides with Ni²⁺/Al³⁺ molar ratios of 1.5 and 3.0 have been synthesized by co-precipitation and studied as catalyst precursors for purification of CO-containing gas-mixtures by means of CO oxidation to CO₂ and conversion of CO by water vapor (water-gas shift reaction). The influence of the alkali additives (K⁺ ions) on the water-gas shift activity has been also examined. It was established that the catalytic activity of both reactions increases with the temperature and the nickel content. Hypothetic schemes are proposed about activation of the catalysts in the WGSR and CO oxidation including redox Ni²⁺ ? Ni³⁺ transition on the catalyst surface. The activity in WGSR is positively affected by the presence of potassium promoter, depending on its amount. The sample with higher nickel loading is the most effective catalyst as for CO oxidation as well as for WGSR at intermediate temperatures after potassium promotion.