Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones

The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM.

Comparative evaluation of 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)2H-tetrazolium, monosodium salt (WST-8) rapid colorimetric assays for antimicrobial susceptibility testing of staphylococci and ESBL-producing clinical isolates

A new generation of water soluble tetrazolium salts have recently become available and in this study we compared a colorimetric assay developed using one of these salts, 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8), with a previously developed 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide(XTT) colorimetric assay to determine which agent is most suitable for use as a colorimetric indicator in susceptibility testing. The MICs of 6 antibiotics were determined for 33 staphylococci using both colorimetric assays and compared with those obtained using the British Society for Antimicrobial Chemotherapy reference broth microdilution method. Absolute categorical agreement between the reference and test methods ranged from 79% (cefuroxime) to 100% (vancomycin) for both assays. No minor or major errors occurred using either assay with very major errors ranging from zero (vancomycin) to seven (cefuroxime). Analysis of the distribution of differences in the 1092 dilution MIC results revealed overall agreement, within the accuracy limits of the standard test ( 1 1092 dilution), using the XTT and WST-8 assays of 98% and 88%, respectively. Further studies on 31 ESBL-producing isolates were performed using the XTT method with absolute categorical agreement ranging from 87% (nitrofurantoin) to 100% (ofloxacin and meropenem). No errors were noted for either ofloxacin or meropenem with overall agreement of 91%. The data suggests that XTT is more reliable and accurate than WST-8 for use in a rapid antimicrobial susceptibility test. (c) 2007 Elsevier B.V. All rights reserved.

Comparative evaluation of 2,3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8) rapid colorimetric assays for antimicrobial susceptibility testing of staphylococci and ESBL-producing clinical isolates

A new generation of water soluble tetrazolium salts have recently become available and in this study we compared a colorimetric assay developed using one of these salts, 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8), with a previously developed 2,3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) colorimetric assay to determine which agent is most suitable for use as a colorimetric indicator in susceptibility testing. The MICs of 6 antibiotics were determined for 33 staphylococci using both colorimetric assays and compared with those obtained using the British Society for Antimicrobial Chemotherapy reference broth microdilution method. Absolute categorical agreement between the reference and test methods ranged from 79% (cefuroxime) to 100% (vancomycin) for both assays. No minor or major errors occurred using either assay with very major errors ranging from zero (vancomycin) to seven (cefuroxime). Analysis of the distribution of differences in the log2 dilution MIC results revealed overall agreement, within the accuracy limits of the standard test (± 1 log2 dilution), using the XTT and WST-8 assays of 98% and 88%, respectively. Further studies on 31 ESBL-producing isolates were performed using the XTT method with absolute categorical agreement ranging from 87% (nitrofurantoin) to 100% (ofloxacin and meropenem). No errors were noted for either ofloxacin or meropenem with overall agreement of 91%. The data suggests that XTT is more reliable and accurate than WST-8 for use in a rapid antimicrobial susceptibility test.

Photophysical and Electrochemical Investigations on Photoconducting Poly(6-tert-butyl-3,4-dihydro-2H- 1,3-benzoxazine)

Poly(6-tert-butyl-3,4-dihydro-2H-1,3-benzoxazine) was synthesized by thermally activated cationic ring opening polymerization. The structure of the polymer was confirmed by spectral and thermal studies. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were estimated using cyclic voltammetry and optical absorption. Modulated photocurrent measurement technique was employed to study the spectral and field dependence of photocurrent. Photocurrent of the order of 1.5 micro A/m2 was obtained for polymer at a biasing electric field of 40 V/mico m.

Double coupling reactions of 3,4-bis(stannyl)furanone: facile preparation of diaryl- and dibenzylfuranones

The palladium-catalyzed cross-coupling reaction of 3,4-bis(tributylstannyl)furan-2(5H)-one using chelating ligand or polar solvent gives mixtures of single and double coupled products, even when one equivalent of halide coupling partner is used. After optimization, the double coupling reaction was shown to be general, with the use of two equivalents of aryl iodides giving 3,4-disubstituted furanones, The reaction using benzyl bromides proceeds at lower temperatures than the corresponding coupling using aryl iodides, giving dibenzylfuranones. The methodology has been exemplified in a synthesis of (+/-)-hinokinin.

Intramolecular Diels-Alder furan-mediated synthesis of 8-aryl-3, 4-di-hydroisoquinolin-1(2H)-ones, convenient precursors of indeno[1,2,3-ij]isoquinolines

We describe herein preliminary studies on the Intramolecular Diels-Alder Furan-Mediated Synthesis of 8-Aryl-3, 4-di-hydroisoquinolin-1(2H)-ones that constitutes a new, formal synthesis of Indeno[1,2,3-ij]isoquinolines.

6-Alkyl-3,4-dihydro-2H-pyrans: Chemical Secretion Compounds in Neotropical Harvestmen

The defensive, secretions, of five neotropical) species of harvestmen, (Opiliones: Gonyleptidae) from the Brazilian Atlantic Forest were analyzed and chemically characterized by GC-MS and NMR Methods. Three of the species, Cobania picea, Roweria virescens, and Serracutisoma proximum, secrete a mixture of 2,3-dimethyl-1,4-benzoquinone and 2-ethyl-3methyl-1,4,4-benzoquinone. The secretions produced,by the Other two species Iporangaia pustulosa and Neosadocus maximus, contain 1-hepten-3-one, 5-methyl-1-hexen-3-one, and 1-(6-butyl-3,4-dihydro-2H-pyran-2-yl)pentanone. (1)as major components, as well as,2,3-dimethyl-1.,4-benzoquinone and 2-ethyl-3 methyl-1,4-benzoquinone as minor,constituents. The. dihydropyran 1-(6-butyl-3,4-dihydro-2H-pyran-2-yl)pentanone (1) is a new natural product, composed of two 1-hepten-3-one, subunits formally linked in a hetero-Diels-Alder reaction. The natural product was proven to be racemic, and its biogenetic origin is discussed.

Spectroscopic Investigation on the Formation of a Dinuclear Me(2)SO-Ru(2)-Mercaptopyridine Bridged Complex: [Ru(2)Cl(3)(mu-pyS)(mu-dmso)(dmso)(4)]center dot 2H(2)O

A dinuclear ruthenium(II) complex double-bridged by an N-aromatic ligand 2-mercaptopyridine (2-pyridinethiol or 2-pyridyl mercaptan) and a methyl sulfoxide (dmso) have been characterized by X-ray crystallography. The reported compound with formula [Ru(2)Cl(3) (mu-pyS)(mu-dmso)(dmso)(4)] center dot 2H(2)O, [C(15)H(36)Cl(3)NO(7)S(6)Ru(2)] (P2/c, a = 13.8175(2) angstrom, b = 10.5608(2) angstrom, c = 21.3544 (3) angstrom, beta = 106.090(1)degrees, V = 2,994.05(8) angstrom(3), Z = 4) represents a seven-membered ring system with both rutheniums in an octahedral geometry. All the hydrogen bonds (C-H-Cl) and the van der Waals contacts give rise to three-dimensional network in the structure and add stability to the dinuclear compound. To our knowledge, this is the first time that the formation of a dinuclear ruthenium(II) complex double-bridged by an N-aromatic ligand 2-mercaptopyridine and dmso have been reported. The study also provided valuable insight into bioinorganic chemistry as continuing efforts are being made to develop metal-based cancer chemotherapeutics. A major feature of this paper is the resolution of a double bridged ruthenium structure which contributes to a better understanding of ruthenium reactivity.

Lead(II)-induced formation and coordination of 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one

Cyclization of (n)butyl glyoxylate thiosemicarbazone (HBuTSC) under reflux in the presence of Pb(OAc)(2) led to tile formation of the complex [Pb(HTz)(2)] (H(2)Tz = 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one), which after recrystallization from DMSO afforded the polymer [Pb(Tz)](n), the first example of a Tz(2-) metal complex. (C) 2008 Elsevier B.V. All rights reserved.

3-Hydroxy-4, 5-dimethyl-2 (5 H)-furanone levels in fortified Madeira wines: Relationship to sugar content

The maturation of Madeira wines usually involves exposure to relatively high temperatures and humidity levels >70%, which affect the aroma and flavor composition and lead to the formation of the typical and characteristic bouquet of these wines. To estimate the levels of sotolon [3-hydroxy4,5-dimethyl-2(5 H )-furanone] and their behavior over time, 86 aged Madeira wines samples (1-25 years old), with different sugar concentrations, respectively, 90 g L-1 for Boal, 110 g L-1 for Malvazia, 25 g L -1 for Sercial, and 65 g L-1 for Verdelho varieties, were analyzed. Isolation was performed by liquid-liquid extraction with dichloromethane followed by chromatographic analysis by GC-MS. The reproducibility of the method was found to be 4.9%. The detection and quantification limits were 1.2 and 2.0 µgL-1, respectively. The levels of sotolon found ranged from not detected to 2000 µgL-1 for wines between 1 and 25 years old. It was observed that during aging, the concentration of sotolon increased with time in a linear fashion ( r ) 0.917). The highest concentration of sotolon was found in wines with the highest residual sugar contents, considering the same time of storage. The results show that there is a strong correlation between sotolon and sugar derivatives: furfural, 5-methylfurfural, 5-hydroxymethylfurfural, and 5-ethoxymethylfurfural. These compounds are also well correlated with wine aging. These findings indicate that the kinetics of sotolon formation is closely related with residual sugar contents, suggesting that this molecule may come from a component like sugar.

Effect of the synthetic coumarin, ethyl 2-oxo-2H-chromene-3-carboxylate, on activity of Crotalus durissus ruruima sPLA2 as well as on edema and platelet aggregation induced by this factor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Crystal structure of bis(acetylacetonato)-bis(3-methylpyridine)-nickel(II) dihydrate, Ni(C6H7N)(2)(C5H7O2)(2)center dot 2H(2)O

C22H32N2NiO6, triclinic, P (1) over bar (no. 2), a = 8.335(1) angstrom, b = 9.314(1) angstrom, c = 17.045(2) angstrom, alpha = 88.45(1)degrees, beta = 82.12(1)degrees, gamma = 70.296(9)degrees, V = 1233.7 angstrom(3), Z = 2, R-gt(F) = 0.050, wR(ref)(F-2) = 0.177, T = 293 K.

Characterization of PLGA microparticles as a drug carrier for 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one. Ultrastructural study of cellular uptake and intracellular distribution

Here we describe the application of microparticles (MPs) for the delivery and release of the drug a benzopsoralen. We also evaluated the intracellular distribution and cellular uptake of the drug by using an encapsulation technique for therapeutic optimization. MPs containing the compound 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one (psoralen A) were prepared by the solvent evaporation technique, and parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process on the drug's photochemistry, zeta potential, external morphology, and < i > in vitro release behavior were evaluated. The intracellular distribution of MPs as well as their uptake by tissues were monitored. Size distribution studies using dynamic ligh scattering and scanning electron microscopy revealed that the MPs are spherical in shape with a diameter of 1.4 mu m. They present low tendency toward aggregation, as confirmed by their zeta potential (+10.6 mV). The loading efficiency obtained was 75%. As a consequence of the extremely low diffusivity of the drug in aqueous medium, the drug release profile of the MPs in saline phosphate buffer (pH 7.4) was much slower than that obtained in the biological environment. Among the population of peritoneal phagocytic cells, only macrophages were able to phagocytose poly-d,l-lactic-co-glycolic acid (PLGA) MP. The use of psoralen A in association with ultraviolet light (360 nm) revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondria condensation, and swelling of both the granular endoplasmatic reticulum and the nuclear membrane. These results indicate that PLGA MP could be a promising delivery system for psoralen in connection with ultraviolet irradiation therapy (PUVA).