Synthesis of Benzylureas and Related Amine Derivatives via Copper-Catalyzed Three-Component Carboamination of Styrenes.

A direct assembly of secondary benzylureas and related amine derivatives via copper-catalyzed carboamination of styrenes with potassium alkyltrifluoroborates and ureas, anilines, or an amide is reported. Terminal and 1,2-disubstituted alkenes, as well as dienes, participate in this three-component coupling reaction. The reaction mechanism likely involves the addition of an alkyl radical to the styrene, followed by metal-mediated oxidative coupling of the resulting benzylic radical with the amine derivative. Factors that impact substrate reactivity and regioselectivity are discussed.

Synthesis and Biological Evaluation of 3,9-Dioxatetraasteranes as C2-Symmetric HIV-1 Protease Inhibitors and Docking Study.

A series of tetraethyl 2,4,8,10-tetramethyl-6,12-diaryl-3,9-dioxahexacyclo[6.4.0.02,7.04,11.05,10]dodecane-1,5,7,11-tetracarboxylates (simplified as 3,9-dioxatetraasteranes) with C2-symmetric structural characteristics were synthesized through the [2 + 2] photocycloaddition of the diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates. Besides, their anti-human immunodeficiency virus (HIV)-1 activities were evaluated by enzyme-linked immunosorbent assay (ELISA) assay against HIV-1 (IIIB) replication in MT-4 cell culture. The result showed that the tested compounds exhibited potential activates with IC50 values less than 110 nM. Furthermore, docking study was carried out to study the binding mode of these compounds. The results indicated that the overall orientation of the inhibitors in the active site were similar to that of the cyclic urea AHA001 and a hydrogen bond with the protein residues might play a crucial role in their anti-HIV-1 activities. Such results will provide a theoretical foundation for further investigations on the biological activity of 3,9-dioxatetraasteranes.

Synthesis and antitumor evaluation of novel sulfonylcycloureas derived from nitrogen mustard.

A new series of sulfonylcycloureas derivatives have been synthesized and evaluated in vitro for their antitumor activity against four cancer cell lines (A431, Jurkat, U266, and K562). These compounds were prepared by the condensation of several sulfonamides (2a-m) with ethyl bis(2-chloroethyl)carbamate (1a). The relative cytotoxicity of these new derivatives in comparison to chlorambucil is reported.

Desarrollo de una formulación estable de ureasa líquida para la determinación de urea en suero / Development of a stable formulation of liquid urease for determination of serum urea

Introducción: la determinación de urea en suero reviste gran importancia para el diagnóstico clínico de diversas afecciones de origen renal. Los métodos más aplicados para este fin implican el uso de la enzima ureasa por su alta especificidad en la hidrólisis de este analito, entre los cuales el método de Berthelot, emplea la ureasa en el primer paso de la reacción, seguido de una reacción colorimétrica del amoníaco liberado. La presentación de la ureasa en forma líquida es uno de los elementos que hacen más sencillo este proceso, de fácil y rápida ejecución con resultados confiables. Objetivo: desarrollar una solución de ureasa estable, como componente del juego de diagnosticador de urea en suero. Métodos: se diseñó y optimizó la formulación teniendo en cuenta: la concentración de la enzima, las soluciones buffer, los preservos y los compuestos orgánicos polihidroxilados para lograr un producto en forma líquida estable. Se evaluó la especificidad, precisión, linealidad, exactitud (comparación de métodos) y la sensibilidad del método; así como la estabilidad en vida de estante de 2 a 8 °C, por un período de 18 meses. Resultados: se logró un reactivo líquido estable (> 12 meses de 2 a 8 °C), donde el método analítico resultó ser específico y lineal hasta 30 mmol/L de urea (r2= 0,999), sensible, preciso coeficiente de variación, CV< 3 por ciento) y exacto (r³ 0,999), satisfactorio para el uso al que se destina el producto, con calidad analítica comparable con los existentes en el mercado. Conclusiones: el desarrollo de la formulación de ureasa líquida estable, permitirá introducir este componente esencial, en el juego de reactivos de urea que oferta la Industria Nacional al Sistema de Salud de acuerdo con los requisitos vigentes (Reg. 8-2001) para su comercialización(AU)

Introduction: determination of serum urea has great importance for the clinical diagnosis of several renal illnesses. The most implemented methods involve the use of the urease enzyme because of its high specificity for this analyte hydrolysis; the Berthelot method uses urease in the first reaction step followed by colorimetric reaction of the released ammonium. The presentation of urease in liquid form is one of the elements that make this process simpler, of easy and fast application with reliable results. Objective: to develop a stable urease solution as part of the diagnostic set for serum urea. Methods: the adequate formulation was designed and optimized by taking into account the enzyme concentration, the buffer solutions, the preserves and the polyhydroxyled organic compounds to attain a final stable liquid product. The parameters called specificity, precision, linearity, accuracy (comparison of methods) and sensitivity of the method were all evaluated in addition to the shelf life at 2 a 8 °C for 18 months. Results: astable liquid reagent (over 12 months at 2 a 8 °C ) was reached; the analytical method proved to be specific and linear up to 30 mmol/L of urea (r²= 0,999), sensitive, precise, with variation coefficient lower than 3 percent and accurate ((r³ 0,999), satisfactory for the intended use of the product and the analytical quality comparable to that of the already existing products. Conclusions: the development of the stable liquid urease formulation will allow introducing this essential component in the reagent set for urea offered by the national industry to the healthcare system according to the requirements for commercialization (Reg 8-2001)(AU)

Desarrollo de una formulación estable de ureasa líquida para la determinación de urea en suero / Development of a stable formulation of liquid urease for determination of serum urea

INTRODUCCIÓN: la determinación de urea en suero reviste gran importancia para el diagnóstico clínico de diversas afecciones de origen renal. Los métodos más aplicados para este fin implican el uso de la enzima ureasa por su alta especificidad en la hidrólisis de este analito, entre los cuales el método de Berthelot, emplea la ureasa en el primer paso de la reacción, seguido de una reacción colorimétrica del amoníaco liberado. La presentación de la ureasa en forma líquida es uno de los elementos que hacen más sencillo este proceso, de fácil y rápida ejecución con resultados confiables. OBJETIVO: desarrollar una solución de ureasa estable, como componente del juego de diagnosticador de urea en suero. MÉTODOS: se diseñó y optimizó la formulación teniendo en cuenta: la concentración de la enzima, las soluciones buffer, los preservos y los compuestos orgánicos polihidroxilados para lograr un producto en forma líquida estable. Se evaluó la especificidad, precisión, linealidad, exactitud (comparación de métodos) y la sensibilidad del método; así como la estabilidad en vida de estante de 2 a 8 °C, por un período de 18 meses. RESULTADOS: se logró un reactivo líquido estable (> 12 meses de 2 a 8 °C), donde el método analítico resultó ser específico y lineal hasta 30 mmol/L de urea (r2= 0,999), sensible, preciso coeficiente de variación, CV< 3 por ciento) y exacto (r 0,999), satisfactorio para el uso al que se destina el producto, con calidad analítica comparable con los existentes en el mercado. CONCLUSIONES: el desarrollo de la formulación de ureasa líquida estable, permitirá introducir este componente esencial, en el juego de reactivos de urea que oferta la Industria Nacional al Sistema de Salud de acuerdo con los requisitos vigentes (Reg. 8-2001) para su comercialización(AU)

INTRODUCTION: determination of serum urea has great importance for the clinical diagnosis of several renal illnesses. The most implemented methods involve the use of the urease enzyme because of its high specificity for this analyte hydrolysis; the Berthelot method uses urease in the first reaction step followed by colorimetric reaction of the released ammonium. The presentation of urease in liquid form is one of the elements that make this process simpler, of easy and fast application with reliable results. OBJECTIVE: to develop a stable urease solution as part of the diagnostic set for serum urea. Methods: THE ADEQUATE FORMULATION WAS DESIGNED AND OPTIMIZED BY TAKING INTO account the enzyme concentration, the buffer solutions, the preserves and the polyhydroxyled organic compounds to attain a final stable liquid product. The parameters called specificity, precision, linearity, accuracy (comparison of methods) and sensitivity of the method were all evaluated in addition to the shelf life at 2 a 8 °C for 18 months. RESULTS: astable liquid reagent (over 12 months at 2 a 8 °C ) was reached; the analytical method proved to be specific and linear up to 30 mmol/L of urea (r2= 0,999), sensitive, precise, with variation coefficient lower than 3 percent and accurate ((r 0,999), satisfactory for the intended use of the product and the analytical quality comparable to that of the already existing products. CONCLUSIONS: the development of the stable liquid urease formulation will allow introducing this essential component in the reagent set for urea offered by the national industry to the healthcare system according to the requirements for commercialization (Reg 8-2001)(AU)

Synthetic oligoureas of metaphenylenediamine mimic host defence peptides in their antimicrobial behaviour.

Oligomeric ureas of m-phenylenediamine target anionic DMPG (dimyristoylphosphatidylglycerol) and possess promise as antimicrobial agents. Their similar size, shape and hydrophobicity to helical antimicrobial peptides (AMPs) may be important for activity to exist and the ability of these compounds to insert into a well ordered lipid environment.

Diferencias en la actividad de la enzima ureasa entre Cryptococcus neoformans y Cryptococcus gattii / Urease activity in Cryptococcus neoformans and Cryptococcus gattii

Se considera que la capacidad de Cryptococcus neoformans para sintetizarureasa es uno de sus principales factores de virulencia. Desde 2002 se aceptaque la variedad gattii de C. neoformans reúne los atributos necesarios paraconsiderarse como una nueva especie, Cryptococcus gattii. No existenestudios experimentales controlados que comparen el grado de actividadureasa de ambas especies. El objetivo de este trabajo ha sido analizar laproducción de esta enzima en aislamientos de C. neoformans y C. gattii,considerando la distribución en serotipos de los aislamientos y su origen(clínico o ambiental), utilizando un nuevo método semicuantitativoestandarizado. Veinticinco aislamientos de C. neoformans y 19 de C. gattiifueron sembrados en medio líquido de urea de Christensen para determinar laproducción de ureasa por espectrofotometría. Como referencia se determinóla actividad de una unidad de ureasa (jack beans urease®, Sigma) sobre elmismo medio de cultivo y se observó que el 50% de la actividad enzimáticacorrespondía a una densidad óptica de A550 = 0,215. Esta absorbancia permitióclasificar la actividad ureasa para cada aislamiento de Cryptococcus.Los resultados mostraron que bajo las mismas condiciones, estas levaduraspodían agruparse en dos categorías, bajas productoras de ureasa(A550 < 0,215) y altas productoras (A550 >= 0,215). A las 72 horas de incubación,el 76% de los aislamientos de C. neoformans y el 15,8% de los de C. gattiiresultaron altos productores de ureasa. El análisis estadístico mostródiferencias significativas entre ambas especies (p = 0,016). Los resultadosobtenidos muestran que C. neoformans es mayor productor de ureasa queC. gattii(AU)

Urease is an enzyme considered one of the main virulence factors inCryptococcus neoformans. Quantitative differences in urease productionbetween C. neoformans and the new species Cryptococcus gattii have notbeen so far documented. Using a standardized method, 25 isolates ofC. neoformans and 19 of C. gattii were seeded in Christensen urea brothmedium for urease activity detection. Approximately, the 50% of activity ofone unit of commercial jack beans urease (A550 = 0.215) was considered as areference to classified the Cryptococcus in two cathegories, low (A550 < 0.215)or high (A550 >= 0.215) urease producers. After 72 hours of incubation, 76% ofC. neoformans and 15.8% of C. gattii strains were high urease producers(p = 0.016). Based on these results, the species C. neoformans appeared asthe highest urease producer. Other virulence factors should also beinvestigated to explain C. gattii pathogenicity(AU)

Synthesis and serological interactions of H. pylori urease fragment 321-339 n-terminally immobilized on the cellulose.

Antigenic epitopes F8 (SIKEDVQF) and UB-33 (UreB fragment with residues 321-339: CHHLDKSIKEDVQFADSRI) in H. pylori urease that induces neutralizing antibody production were prepared on the cellulose plate from N- to C-terminus using CDMT as a coupling reagent. Reaction of both epitopes with sera of patients with medically confirmed atherosclerosis was studied. Strong, selective reactions of both peptides with some patients sera were observed.

Radical hydroxyalkylation of C-H bond adjacent to nitrogen of tertiary amides, ureas, and amines.

Tertiary amides, ureas, and amines undergo direct intermolecular addition to aldehydes under the Et3B/air conditions, thereby providing a unique and simple means for the radical sp3 C-H transformation of nitrogen-containing molecules.

[Synthesis and study of the properties of water-insoluble products of the interaction of urease and cellulose derivatives]. / Sintez i issledovanie svoistv nerastvorimykh v vode produktov vzaimodeistviia ureazy i proizvodnykh tselliulozy

As a result of reaction of urease with graft copolymer of cellulose and polyglycidyle methacrylate or with carboxymethyl cellulose, products were synthesized, containing about 2% of chemically bound urease. Binding with the cellulose derivatives was accompanied by about two-fold decrease in urease activity. Carboxymethyl cellulose-urease and polyglycidile methacrylate-cellulose-urease might be repeatedly (for 30 cycles) used for hydrolysis of urea; the enzymatic activity of the first compound did not change, but of the second one--was decreased by 30%. Activity of the compounds was not changed after storage within 2 months in 0.1 M phosphate buffer, pH 7.0 at 4 degrees C.