RESUMO
The present study aims at understanding the effect of organic solvents on the specific proteolytic activity and operational stability of asclepain cI in aqueous-organic media, using correlations between geometrical and structural parameters of asclepain cI. These correlations were determined by molecular dynamics (MD) simulations and the secondary structure of the enzyme validated by Fourier-transform Infrared (FTIR) spectroscopy. Asclepain cI exhibited significantly higher catalytic potential in 29 of the 42 aqueous-organic media tested, composed by 0.1 mM TRIS hydrochloride buffer pH 8 (TCB) and an organic solvent, than in buffer alone. Asclepain cI in water-organic miscible systems showed high FTIR spectral similarity with that obtained in TCB, while in immiscible systems the enzyme acquired different secondary structures than in buffer. Among the conditions studied, asclepain cI showed the highest catalytic potential in 50% v/v ethyl acetate in TCB. According to MD simulations, that medium elicited solvation and flexibility changes around the active center of asclepain cI and conducted to a new secondary structure with the active center preserved. These results provide valuable insights into the elucidation of the molecular mechanism of asclepain cI tolerance to organic solvents and pave the way for its future application for the synthesis of peptides in aqueous-organic media.
Assuntos
Simulação de Dinâmica Molecular , Estrutura Secundária de Proteína , Solventes , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Estabilidade EnzimáticaRESUMO
Encapsulation of three superoxide dismutase (SOD) functional mimics, [CuZn(dien)2(µ-Im)(ClO4)2]ClO4 (1), [Cu2(dien)2(µ-Im)(ClO4)2]ClO4 (2) (Im = imidazolate, dien = diethylenetriamine), and [CuZn(salpn)Cl2] (3) (H2salpn = 1,3-bis(salicylideneamino)propane) in mesoporous MCM-41 silica afforded three hybrid catalysts 1@MCM-41, 2@MCM-41 and 3@MCM-41. Spectroscopic and magnetic analyses of these materials confirmed the metal centers of the complexes keep the coordination sphere after insertion into the MCM-41 silica matrix. For the imidazolate-bridged complexes the silica channels restraint the relative orientation of the two metal ions. While 3@MCM-41 shows SOD activity significantly lower than the host-free complex, insertion of the imidazolate-bridged CuZn or Cu2 complexes by ion exchange onto mesoporous MCM-41 silica affords durable and recoverable supported catalysts with much better SOD activity than the free complexes. For confined imidazolate-bridged complexes, 1@MCM-41 and 2@MCM-41, the small pore size of the silica matrix improves the SOD activity more than a host with larger pores. This high SOD activity is attributed to the close-fitting of the complexes into the nanochannels of MCM-41 silica that favors the Cu active site and HImZn(or Cu) group stay in close proximity during catalysis.
Assuntos
Cobre/química , Compostos Organometálicos/química , Dióxido de Silício/química , Superóxido Dismutase/química , Zinco/química , Catálise , Espectroscopia de Ressonância de Spin Eletrônica , Imidazóis/química , Compostos Organometálicos/metabolismo , Espectrofotometria Ultravioleta , Superóxido Dismutase/metabolismoRESUMO
Mebendazole (MBZ), designated as a WHO essential drug, can exist in diverse solid forms and presents low absorption at the gastrointestinal level. Considering the potential of cyclodextrins to enhance the solubility and permeability of drugs, inclusion complexes of polymorphs A and C of MBZ with ßcyclodextrin were obtained. The characterization of the complexes in solid state was performed by using a combination of experimental techniques including Fourier transform infrared spectroscopy, powder X-ray diffractometry and solid state nuclear magnetic resonance. Moreover, the effect of the binary complexes on their physical stability was evaluated. In addition, for a complete characterization of polymorphs A and C, one dimensional spectra and correlation nuclear magnetic resonance experiments were employed. Our physical studies showed that the inclusion complexes were new crystalline forms that induced shifts and broadening in the infrared and nuclear spectra. A molecular modelling analysis performed on the inclusion modes, demonstrated that the most favourable structure for the complex was the head down orientation. Moreover, the intermolecular interactions calculated for the complex with the atoms in molecules theory are in good agreement with the spectroscopic results. The inclusion complexes exhibited an increment of solubility in simulated physiological media. Furthermore, it was demonstrated that the complex formation did not affect the physical stability of the polymorphs.
Assuntos
Anti-Helmínticos/química , Mebendazol/química , beta-Ciclodextrinas/química , Cristalização , Modelos MolecularesRESUMO
A sulfonamide 1-tosyl-1-H-benzo(d)imidazol-2-amine (TBZA) and three new complexes of Co(II), Cu(II), and Zn(II) have been synthesized. The compounds have been characterized by elemental analyses, FTIR, 1H, and 13C-NMR spectroscopy. The structure of the TBZA, and its Co(II) and Cu(II) complexes, was determined by X-ray diffraction methods. TBZA and its Co(II) complex crystallize in the triclinic P-1 space group, while the Cu(II) complex crystallizes in the monoclinic P21/c space group. Antifungal activity was screened against eight pathogenic yeasts: Candida albicans (DMic 972576), Candida krusei (DMic 951705), Candida glabrata (DMic 982882), Candida tropicalis (DMic 982884), Candida dubliniensis (DMic 93695), Candida guilliermondii (DMic 021150), Cryptococcus neoformans (ATCC 24067), and Cryptococcus gattii (ATCC MYA-4561). Results on the inhibition of various human (h) CAs, hCA I, II, IV, VII, IX, and XII, and pathogenic beta and gamma CAs are also reported.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Cryptococcus/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Cobalto/química , Cobalto/farmacologia , Cobre/química , Cobre/farmacologia , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/farmacologia , Zinco/química , Zinco/farmacologiaRESUMO
Three salts of 5-amino-2-sulfonamide-1,3,4-thiadiazole (Hats) were prepared and characterized by physico-chemical methods. The p-toluensulfonate, the methylsulfonate, and the chlorhydrate monohydrate salts of Hats were evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) and as anticonvulsants and diuretics, since many CAIs are clinically used as pharmacological agents. The three Hats salts exhibited diuretic and anticonvulsant activities with little neurotoxicity. The human (h) isoforms hCA I, II, IV, VII, IX, and XII were inhibited in their micromolar range by these salts, whereas pathogenic beta and gamma CAs showed similar, weak inhibitory profiles.
Assuntos
Acetazolamida/análogos & derivados , Anticonvulsivantes/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Diuréticos/farmacologia , Sulfonamidas/química , Tiadiazóis/farmacologia , Anticonvulsivantes/química , Inibidores da Anidrase Carbônica/química , Diuréticos/química , Humanos , Isoenzimas/antagonistas & inibidores , Tiadiazóis/químicaRESUMO
Euphorbia serpens Kunth var. microphylla Müll. Arg. (Euphorbiaceae), Amaranthus muricatus (Moq.) Hieron. (Amaranthaceae) y Lithraea molleoides (Vell.) Engl. (Anacardiaceae) son plantas usadas tradicionalmente en el Cono Sur de América como diuréticas. Las dos primeras son hierbas denominadas vulgarmente "yerbas meonas", mientras que la última, un árbol perennifolio, es conocido como "molle de beber" o "molle dulce". El objeto de este trabajo es caracterizar los extractos acuosos de estas drogas vegetales, identificando y cuantificando manitol por HPLC, debido a que este alcohol sería el principal responsable de la actividad diurética que han mostrado las tres plantas. Se realizó además, la caracterización fisicoquímica de las especies vegetales por comparación de los espectros de FT-IR. Los cromatogramas obtenidos por HPLC muestran picos con tiempos de retención a 35,44 min (estándar) característicos para manitol, y el área por debajo de las respectivas curvas permitió establecer concentraciones respecto a materia seca entre 23,056 g Kg-1 en E. serpens var. microphylla; 4,638 g Kg-1 en L. molleoides; y 2,080 g Kg-1 en A. muricatus. Estas cifras explican las diferencias en la potencia diurética descripta en la bibliografía para las especies en estudio. Los espectros IR presentan una relación de áreas de las bandas CO/CH que resultó distintiva para las dos especies (8,42 para E. serpens var. microphylla; 9,28 para A. muricatus; y 11,18 para L. molleoides). El valor mayor correspondiente a L. molleoides indica mayor cantidad de compuestos oxigenados. Los datos espectrales obtenidos permiten contribuir a la caracterización de los extractos acuosos de estas especies y aportan datos para un control de calidad efectivo de las drogas vegetales y los medicamentos herbarios que los contengan en su formulación. (AU)
Assuntos
Humanos , Euphorbiaceae , Amaranthaceae , Anacardiaceae , Diuréticos , Argentina , CromatografiaRESUMO
Diversas especies de Passiflora L. (Passifloraceae) son usadas en medicina tradicional en el tratamiento de la ansiedad, el insomnio y otros trastornos nerviosos. De ellas han sido aisladas varias C-glicosilflavonas. En este trabajo se determinó la presencia de C-glicosilflavonas en Passiflora caerulea L. y P. foetida L., por medio de HPLC y se utilizó FTIR en forma comparativa, con el objeto de hacer un aporte al control de calidad y caracterizar los extractos acuoso y metanólico de ambas especies. Los cromatogramas de HPLC de ambos extractos mostraron tiempos de retención característicos a 12,10 min (vitexina), 17,94 min (isovitexina), 19,93 min (orientina) y 25,11 min (isoorientina), con espectros UV característicos. P. caerulea presentó las cuatro C-glicosilflavonas mencionadas, mientras que P. foetida careció solo de isoorientina en el extracto acuoso y únicamente presentó vitexina e isovitexina en el extracto metanólico. En la zona de la "huella dactilar" de los perfiles FTIR se observaron diferencias cualitativas sustanciales. P. foetida presentó una banda a 1.250 cm-1, que no se detectó en P. caerulea. En esta última la relación de áreas CO/CH del extracto acuoso fue de 3,87; mientras que para P. foetida fue de 1,58; en el extracto metanólico la relación de áreas CO/CH resultó 17,09 para P. caerulea y 15,40 para P. foetida. Estos datos espectrales aportan herramientas que pueden facilitar la caracterización de ambas especies durante el control de calidad de las drogas crudas y de los medicamentos herbarios que las contengan en su formulación. (AU)
Assuntos
Humanos , Plantas Medicinais , Extratos Vegetais , Passifloraceae , Argentina , Cromatografia , Medicina TradicionalRESUMO
Mebendazole mesylate monohydrate, a new stable salt of mebendazole (MBZ), has been synthesized and fully characterized. It was obtained from recrystallization of MBZ forms A, B, or C in diverse solvents with the addition of methyl sulfonic acid solution. The crystal packing is first organized as a two-dimensional array consisting of rows of alternating MBZ molecules linked to columns of mesylate ions by hydrogen bonds. The three-dimensional structure is further developed by classical intermolecular interactions involving water molecules. In addition, nonclassical contacts are also found. The vibrational behavior is consistent with the crystal structure, the most important functional groups showing shifts to lower or higher frequencies in relation to the MBZ polymorphs. Thermal analysis indicates that the compound is stable up to 50°C. Decomposition occurs in five steps. Solubility studies show that the title compound presents a significant higher performance than polymorph C. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3528-3538, 2013.
Assuntos
Mebendazol/química , Mesilatos/química , Cristalização/métodos , Ligação de Hidrogênio , Solubilidade , Soluções/química , Solventes/químicaRESUMO
Se presenta por primera vez un estudio sobre la frecuencia de litiasis urinaria en la ciudad de San Luis, Argentina, a partir de datos de espectroscopía infrarroja. Se analizaron los espectros infrarrojos de 169 cálculos urinarios provenientes de centros sanitarios tanto públicos como privados. Los componentes químicos encontrados fueron oxalato de calcio monohidrato, uratos, fosfato de calcio, fosfato amónico magnésico hexahidrato y de composición mixta. El análisis cuantitativo de los datos, utilizando la estadística descriptiva, permitió determinar el tipo de composición litiásica más frecuente en el total de los sujetos y la distribución de los tipos encontrados según sexo y edad. La frecuencia de oxalato de calcio monohidrato y de uratos fue mayor en hombres que en mujeres correspondiendo a una franja etaria entre 21 y 60 años y entre 41 y 70 años, respectivamente. Esta relación se invierte en los fosfatos de calcio o magnesio presentando mayor incidencia en mujeres. Los cálculos de composición mixta se distribuyen de igual manera entre hombres y mujeres.
A study dealing with urinary lithiasis frequency in San Luis city, Argentina, applying infrared spectroscopy is reported for the first time. The infrared spectra of 169 urinary stones provided by public and private sanitary centers were analyzed. The most frequent chemical components found were calcium oxalate monohydrate, urates, calcium phosphate, magnesium ammonium phosphate hexahydrate and mixed compositions. Quantitative data analysis, performed by descriptive statistics enabled the determination of the most frecuent lithiasic composition for all the cases, as well as its distribution according to the corresponding age and sex. Calcium oxalate monohydrate and urates were more frequently found in men than in women ranging between 21- 60 and between 41-70 years old, respectively. The inverse ratio is determined for calcium or magnesium phosphates, women being the most affected. Stones with mixed composition showed the same incidence in women and men.
Assuntos
Humanos , Espectroscopia de Luz Próxima ao Infravermelho/estatística & dados numéricos , Urolitíase/urina , Argentina , Doenças Urológicas/urina , Litíase/químicaRESUMO
Mebendazole (MBZ) is a common benzimidazole anthelmintic that exists in three different polymorphic forms, A, B, and C. Polymorph C is the pharmaceutically preferred form due to its adequated aqueous solubility. No single crystal structure determinations depicting the nature of the crystal packing and molecular conformation and geometry have been performed on this compound. The crystal structure of mebendazole form C is resolved for the first time. Mebendazole form C crystallizes in the triclinic centrosymmetric space group and this drug is practically planar, since the least-squares methyl benzimidazolylcarbamate plane is much fitted on the forming atoms. However, the benzoyl group is twisted by 31(1) degrees from the benzimidazole ring, likewise the torsional angle between the benzene and carbonyl moieties is 27(1) degrees. The formerly described bends and other interesting intramolecular geometry features were viewed as consequence of the intermolecular contacts occurring within mebendazole C structure. Among these features, a conjugation decreasing through the imine nitrogen atom of the benzimidazole core and a further resonance path crossing the carbamate one were described. At last, the X-ray powder diffractogram of a form C rich mebendazole mixture was overlaid to the calculated one with the mebendazole crystal structure.