Self-assembly structures of 1H-indazoles in the solution and solid phases: a vibrational (IR, FIR, Raman, and VCD) spectroscopy and computational study.

1H-indazoles are good candidates for studying the phenomena of molecular association and spontaneous resolution of chiral compounds. Thus, because the 1H-indazoles can crystallize as dimers, trimers, or catemers, depending on their structure and the phase that they are in, the difficulty in the experimental analysis of the structure of the family of 1H-indazoles becomes clear. This difficulty leads us to contemplate several questions: How can we determine the presence of different structures of a given molecular species if they change according to the phase? Could these different structures be present in the same phase simultaneously? How can they be determined? To shed light on these questions, we outline a very complete strategy by using various vibrational spectroscopic techniques that are sensitive (VCD) and insensitive (IR, FIR, and Raman) towards the chirality, together with quantum chemical calculations.

Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloproteinases.

Seven N-unsubstituted curcuminoid pyrazoles have been synthesized from the corresponding beta-diketones (including curcumin). We evaluated the possibility of curcuminoid pyrazoles regulating the activity of matrix metalloproteinases (MMPs) by human intestinal epithelial cells in vitro. Zymographic analysis revealed that three compounds significantly down-regulated MMP-9 activity on inflammation-induced intestinal epithelial cells, making them original candidates for the treatment of inflammatory bowel disease (IBD).

Fluorescence spectroscopy and amplified spontaneous emission (ASE) of phenylimidazoles: predicted vibronic coupling along the excited-state intramolecular proton transfer in 2-(2'-hydroxyphenyl)imidazoles.

Methylation at the 1N position of 2-phenylimidazole provides the shortest wavelength for a liquid-state laser dye reported to date; that is, the 1-methyl-2-phenylimidazole molecule in cyclohexane solution yields amplified spontaneous emission (ASE) with a peak wavelength at 314.5 nm and a constant laser gain value of 5 cm(-1) from 310 to 317 nm. Methyl substitution in this case favors the appearance of laser action (owing to a torsion-vibrational mechanism) in cyclohexane as compared with the nonmethylated species which does not exhibit ASE in this solvent. The 2-(2'-hydroxyphenyl)imidazole molecules give rise to ASE with high gain values (ca. 9 cm(-1)) at 450 and 466 nm. The mechanism of population inversion is understood in terms of a vibronic coupling between the hydroxyl stretching motion and the torsional vibration of the phenyl and imidazole rings. The proton-transfer spectroscopy of 2-(2'-hydroxyphenyl)imidazoles is studied in dioxane, cyclohexane, dimethyl sulfoxide, methanol, and water. The greater the acidity of the solvent the greater the disruption of the intramolecular hydrogen bond; solvent acidity is the main parameter which favors formation of the open-form species in the ground electronic state. Methyl substitution at the 1N position favors formation of the open species for 2-hydroxyphenylimidazoles in the ground electronic state, which decreases their own capacity to undergo ASE. Low-temperature absorption spectroscopy confirms aggregation processes for 2-(2'-hydroxyphenyl)imidazoles in solution. In accordance with X-ray analyses in the solid phase, these molecules form associations through intermolecular chains of the type N-H...O or O-H...N.

Determining hydrogen-bond strengths in the solid state by NMR: the quantitative measurement of homonuclear J couplings.

Hydrogen-bonding strengths in the solid state are quantitatively determined by the accurate measurement of 15N-15N J couplings using a straightforward 2D MAS NMR spinecho approach.

Study on the mutagenicity of nifurtimox and eight derivatives with the L-arabinose resistance test of Salmonella typhimurium.

The mutagenicity of nifurtimox (nfx) and 8 nfx analogues has been investigated with the L-arabinose forward-mutation assay of Salmonella typhimurium. The nfx analogues tested were obtained by replacing the 3-methyl-4-yl-tetrahydro-1,4-thiazine-1,1-dioxide group of the parent compound with the following other groups: indazol-1-yl (1); pyrazol-1-yl (2); benzimidazol-1-yl (3); 1,2,4-triazol-4-yl (4); 1-methyl-3-methylthio-1,2,4-triazol-4-yl-5-thione (5); 3,5-bis(methylthio)-1,2,4-triazol-4-yl (6); 1-adamantyl (7); 4,6-diphenylpyridin-1-yl-2-one (8). The mutagenic activity of each chemical was determined by the standard plate-incorporation test, in the presence or absence of the S9 activation mixture. The 9 compounds were mutagenic and exhibited linear dose-mutagenic response relationships. They were direct-acting mutagens and showed a nearly 1000-fold range in mutagenic potency from chemical 1 to nfx. In most cases, the addition of S9 mixture to the test plates decreased the mutagenicity of compounds. This effect was particularly noticeable in the case of chemicals 1-3, 5 and 7 where a more than 70% decrease in mutagenic activity was observed in the presence of the S9 mixture. The mutagenic potency of compounds in the Ara test showed a negative linear correlation with previously reported antitrypanosomal activity. Thus, chemicals 6 and 8 with in vitro activities against Trypanosoma cruzi clearly superior to that of nfx showed 2 of the lowest mutagenic potencies in the Ara test and these were only somewhat higher than the mutagenicity of the reference drug.

Mutagenicity study on pyrazole, seven pyrazole derivatives, and two nitroimidazoles with the L-arabinose resistance test of Salmonella typhimurium.

The mutagenicity of pyrazole and seven pyrazole derivatives (4-nitropyrazole, 4-bromopyrazole, 1-methyl-4-nitropyrazole, 3,5-dimethyl-4-nitropyrazole, 1-methyl-4-bromopyrazole, 4,4'-dinitro-1, 1'-methylene-dipyrazole and 4,4'-dibromo-1,1'-methylene-dipyrazole) has been investigated with the L-arabinose forward mutation assay of Salmonella typhimurium. Two nitroimidazoles (1-methyl-5-nitroimidazole and metronidazole) were included as reference drugs. The mutagenicity of each chemical was determined by both preincubation and liquid tests, in the presence or absence of S9 microsomal fraction. The mutagenic response was expressed as the absolute number of L-arabinose resistant mutants growing in selective plates, supplemented with traces of D-glucose. Strain BA13 with a wildtype lipopolysaccharide barrier was used as a comparison to the deep rough derivative BA9. No mutagenic effect was detected with pyrazole and two of its derivatives, 1-methyl-4-bromopyrazole and 4,4'-dibromo-1,1'-methylene-dipyrazole. The other five pyrazole derivatives were mutagenic to different degrees, although their mutagenic potencies were always considerably lower than those of the two nitroimidazoles. The results suggest that 4-nitropyrazoles, as well as 4,4'-dinitro-1, 1'-methylene-dipyrazoles, should be investigated further as alternatives to, or even substitutes for, the currently used nitroimidazoles.

Carbonic anhydrase activators. XV. A kinetic study of the interaction of bovine isozyme II with pyrazoles, bis- and tris-azolyl-methanes.

A series of eighteen substituted pyrazoles, bis- and tris-azolyl-methanes or ethanes was investigated for their interaction with the zinc enzyme carbonic anhydrase (CA). Several types of activities were detected, generally as CA activators, but Ca inhibitory properties were also discovered for the very sterically-demanding derivatives of these series. Kinetic determinations by a stopped-flow technique for carbon dioxide hydration reaction allowed the determination of Michaelis-Menten constants, which are identical in the absence or in the presence of these modulators, proving a noncompetitive mechanism of activation-inhibition. MNDO calculations were used with moderate success to explain the biological results.

Carbonic anhydrase activators. VII. Isozyme II activation by bisazolyl-methanes, -ethanes and related azoles.

A correlation was found between the carbonic anhydrase II activating power and the pKa values for a series of azoles, bisazolylmethanes and bisazolylethanes. Strong activations were found for compounds with pKa's in the interval 6.5-8.0. The mechanism of action for such activators is discussed.

Research for new antichagasic drugs.

A series of ten 1-[(5-nitrothenylidene)amino]azoles has been synthesized by the reaction of 5-nitrothiophene-2-carbaldehyde with 1-aminopyrazole, 1-aminoimidazole, 1- and 4- amino-1,2,4-triazoles, 1-aminoindole, 1- and 2-aminoindazoles, 1-aminobenzimidazole and 1- and 2-aminobenzotriazoles. Physical data, spectroscopic characteristics and biological properties of all the derivatives have been examined. The antiprotozoal activity has been tested against Trypanosoma cruzi, comparative to Nifurtimox (Lampit).

Tratamiento alternativo de la ambliopía estrábica: comparación con el tratamiento clásico: evaluación preliminar / Alternative treatment of the strabic amblyopia: comparison between classic treatment: preliminary assessment

Introducción: Estudios previos demuestran posibilidades de un tratamiento alternativo de la Ambliopía Estrábica. Material y Método: Es un estudio prospectivo con una distribución homogénea estratificada estudiamos el éxito del tratamiento tradicional de la ambliopía con oclusión total (15:2) en comparación con un tratamiento alternativo que estimula áreas paracentrales de la retina del ojo ambliope con un filtro azul durante 1 hora diaria. Entran al estudio niños de 3 a 7 años de edad, sin tratamiento previo. Los parámetros de medición son la agudeza visual, la fijación retinal del ojo ambliope y los Potenciales Evocados Visuales. La primera evaluación se efectúa después de 6 meses de tratamiento. Resultados: De los primeros 9 pares de niños de iguales condiciones iniciales (=18 pacientes), en 7 pares la comparación de agudeza visual termina en favor del tratamiento alternativo. En 2 pares la agudeza visual mejoró en mayor grado con el tratamiento clásico. La fijación mejoró en los 9 pacientes con tratamiento alternativo y sólo en 5 casos con tratamiento clásico. Conclusiones: La evaluación preliminar con el test de Wilcoxon para diferencias de pares en los primeros 18 niños muestra una tendencia estadística hacia mejores resultados con el tratamiento alternativo, lo cual valida la continuación del estudio

Hemorragias retinales del polo posterior en recién nacidos de término con parto normal de término con parto normal y sus secuelas a 4 años / Retinal hemorrhages of posterior pole in term newborn with normal delivery and its sequeles after 4 years

Se estudiaron prospectivamente 374 recién nacidos de término, en el Hospital San Juan de Dios, Santiago, Chile, se realizó un examen de fondo de ojo, antes de las 48 horas de vida, con oftalmoscopía directa, previamente dilatados con Tropicamida al 0,5 por ciento, en busca de hemorragias retinales (H.R.) de polo posterior (fundamentalmente papila y mácula). Las H.R. son más frecuentes en primíparas y tienen una frecuencia de 23,5 por ciento. Se controlaron prospectivamente los pacientes con Fondo de Ojo, estudio sensorio motor y agudeza visual hasta los 4 años de edad, para restablecer si existe relación con tropía y/o ambliopía. No hay relación entre la presencia de H.R. de polo posterior al nacer en el grupo estudiado y el desarrollo de tropía y/o ambliopía. El seguimiento es difícil por la no asistencia a los controles de los pacientes