Estructuras relacionadas con los benzomorfanos: síntesis de tienomorfanos

[spa] En 1947, apareció por primera vez en la bibliografía química el nombre de 6,7-benzomorfano, estructura relacionada con la de la morfina, siendo la sustancia base de una familia de analgésicos sintéticos ampliamente estudiados hoy día por diversos grupos de investigadores de todo el mundo. En nuestro Departamento se ha planteado la posibilidad de una sustitución isostérica de anillo bencénico de dichos compuestos por anillos heterocíclicos, en particular por el tiofeno, con la pretensión de obtener nuevos productos con poder analgésico similar a los opiáceos y con el deseo de lograr que no presenten efectos secundarios indeseables, así como ayudar a elucidar el mecanismo de acción de dicha familia de fármacos. Desde el punto de vista puramente químico sintético que nos ocupa de un modo directo, nuestro objetivo ha sido poner a punto un nuevo camino de síntesis original que obviara algunas de las dificultades que surgen por los caminos clásicos

Perturbation of the dimer interface of triosephosphate isomerase and its effect on trypanosoma cruzi

Chagas disease affects around 18 million people in the American continent. Unfortunately, there is no satisfactory treatment for the disease. The drugs currently used are not specific and exert serious toxic effects. Thus, there is an urgent need for drugs that are effective. Looking for molecules to eliminate the parasite, we have targeted a central enzyme of the glycolytic pathway: triosephosphate isomerase (TIM). The homodimeric enzyme is catalytically active only as a dimer. Because there are significant differences in the interface of the enzymes from the parasite and humans, we searched for small molecules that specifically disrupt contact between the two subunits of the enzyme from Trypanosoma cruzi but not those of TIM from Homo sapiens (HTIM), and tested if they kill the parasite

Perturbation of the Dimer Interface of Triosephosphate Isomerase and its Effect on Trypanosoma cruzi

Most of the enzymes of parasites have their counterpart in the host. Throughout evolution, the three-dimensional architecture of enzymes and their catalytic sites are highly conserved. Thus, identifying molecules that act exclusively on the active sites of the enzymes from parasites is a difficult task. However, it is documented that the majority of enzymes consist of various subunits, and that conservation in the interface of the subunits is lower than in the catalytic site. Indeed, we found that there are significant differences in the interface between the two subunits of triosephosphate isomerase from Homo sapiens and Trypanosoma cruzi (TcTIM), which causes Chagas disease in the American continent. In the search for agents that specifically inhibit TcTIM, we found that 2,2′-dithioaniline (DTDA) is far more effective in inactivating TcTIM than the human enzyme, and that its detrimental effect is due to perturbation of the dimer interface. Remarkably, DTDA prevented the growth of Escherichia coli cells that had TcTIM instead of their own TIM and killed T. cruzi epimastigotes in culture. Thus, this study highlights a new approach base of targeting molecular interfaces of dimers

Estructuras relacionadas con los benzomorfanos: síntesis de tienomorfanos

En 1947, apareció por primera vez en la bibliografía química el nombre de 6,7-benzomorfano, estructura relacionada con la de la morfina, siendo la sustancia base de una familia de analgésicos sintéticos ampliamente estudiados hoy día por diversos grupos de investigadores de todo el mundo. En nuestro Departamento se ha planteado la posibilidad de una sustitución isostérica de anillo bencénico de dichos compuestos por anillos heterocíclicos, en particular por el tiofeno, con la pretensión de obtener nuevos productos con poder analgésico similar a los opiáceos y con el deseo de lograr que no presenten efectos secundarios indeseables, así como ayudar a elucidar el mecanismo de acción de dicha familia de fármacos. Desde el punto de vista puramente químico sintético que nos ocupa de un modo directo, nuestro objetivo ha sido poner a punto un nuevo camino de síntesis original que obviara algunas de las dificultades que surgen por los caminos clásicos

Estructuras relacionadas con los benzomorfanos: síntesis de tienomorfanos

En 1947, apareció por primera vez en la bibliografía química el nombre de 6,7-benzomorfano, estructura relacionada con la de la morfina, siendo la sustancia base de una familia de analgésicos sintéticos ampliamente estudiados hoy día por diversos grupos de investigadores de todo el mundo. En nuestro Departamento se ha planteado la posibilidad de una sustitución isostérica de anillo bencénico de dichos compuestos por anillos heterocíclicos, en particular por el tiofeno, con la pretensión de obtener nuevos productos con poder analgésico similar a los opiáceos y con el deseo de lograr que no presenten efectos secundarios indeseables, así como ayudar a elucidar el mecanismo de acción de dicha familia de fármacos. Desde el punto de vista puramente químico sintético que nos ocupa de un modo directo, nuestro objetivo ha sido poner a punto un nuevo camino de síntesis original que obviara algunas de las dificultades que surgen por los caminos clásicos

Red organic light-emitting radical adducts of carbazole and tris(2,4,6-trichlorotriphenyl)methyl radical that exhibit high thermal stability and electrochemical amphotericity

10 pages, 3 figures.-- PMID: 17824646 [PubMed].Supprting information (General procedures, Cyclic voltammograms, EPR spectra, DSC analysis, Computational data, 1H NMR spectra and Infrared spectra, 24 pages) available at: http://pubs.acs.org/doi/suppl/10.1021/jo0708846/suppl_file/jo0708846-file002.pdfSynthesis and characterization of new carbazolyl derivatives with a pendant stable radical of the TTM (tris-2,4,6-trichlorophenylmethyl radical) series are reported. The EPR spectra, electrochemical properties, absorption spectra, and luminescent properties of these radical adducts have been studied. All of them show electrochemical amphotericity being reduced and oxidized to their corresponding stable charged species. The luminescence properties of them cover the red spectral band of the emission. The luminescence of the electron-rich carbazole adducts shows the donor-acceptor nature of the excited state. On the other hand, the EPR parameters of these radical adducts show an imperceptible variation with the substituents in the carbazole.Financial support for this research was provided by the Ministerio de Educación y Ciencia (Spain) through Grant No. CTQ2006-15611-C02-02/BQU. S.C. gratefully acknowledges the Generalitat de Catalunya for a predoctoral grant, and M.L. thanks the Institut d´Investigacions Químiques i Ambientals de Barcelona (CSIC) and the European Social Fund for his I3P fellowship. We also thank the EPR service of the Institut d’Investigacions Químiques i Ambientals de Barcelona (CSIC) for recording the EPR spectra.Peer reviewe

Synthesis and non-linear optical and redox properties of 6-nitro-6'-piperidyl-2,2'-bisbenzothiazole: a new type of push–pull molecules

5 pages, 4 figures, 1 scheme, 1 table.-- Available online Dec 6, 2004.The present paper describes the synthesis, the non-linear optical and redox properties of 6-nitro-6'-piperidyl 2,2'-bisbenzothiazole, the first described member of a new family of push–pull structures based in the 2,2'-bisbenzothiazole.This research was supported by the Spanish Ministerio de Educación y Cultura, grants PB96-1491 and BQU2000-0789-C02-02, and the Generalitat de Catalunya, grant 1996SGR 00094.Peer reviewe

Tautomeric enhancement of the hyperpolarizability in new acridine-benzothiazolylamine based NLO chromophores

The second order NLO response of a new family of acridine-based chromophores is greatly enhanced due to the presence of a tautomeric minor form with high charge-transfer capabilities.7 page(s

Differential Behavior of Amino–Imino Constitutional Isomers in Nonlinear Optical Processes

8 páginas, 6 figuras, 2 esquemas.A detailed study of the “blocked” amino–imino tautomers derived from N-acridine-substituted 2-aminobenzothiazole—and their effect on the nonlinear optical response—is presented. The synthesis, characterization, and nonlinear optical properties of these frozen tautomers, namely, N-methyl-N-(2-nitroacridin-6-yl)-2-aminobenzothia-zole and 3-methyl-N-(7-nitroacridin-3-yl)-2-iminobenzothiazole, are reported. A theoretical model based on valence–bond theory is also proposed and used to analyze the effects of the nuclear configuration corresponding to each frozen tautomer structure. In the present case, the aromatic form and the allylic-anion-like system of the [BOND]N[BOND]C[BOND]N[BOND] group inherent to each isomer are crucial for understanding and analyzing the different responses of each “blocked” tautomer.Financial support from the Spanish Ministerio de Ciencia y Tecnología, DGI projects FIS2008–02238/FIS, CTQ-2006–15611-C02–02, CTQ2008–02856/BQU, MAT2008–06522-C02–02 and, in part, from the Generalitat de Catalunya projects 2005SGR-000697 and 2005SGR-00111 are fully acknowledged. We also acknowledge to the staff of NMR Spectroscopy Service of the Servei Cientifico-tècnics of the Universitat de Barcelona, in special to Ma Teresa González, for the assistance in the 2D experiments.Peer reviewe

Stable radical cores: a key for bipolar charge transport in glass forming carbazole and indole derivatives

Stable radical adducts of the TTM series bearing carbazolyl or indolyl fragments show bipolar transport properties with mobility values among the highest detected in glassy small molecules. Bipolarity is attributed to the radical character, while the heterocyclic ring confers the adducts the glassy morphological states and the non-dispersive regimes for charge transport.Peer reviewe