RESUMO
The terpenoid (-)-Istanbulin A is a natural product isolated from Senecio filaginoides DC, one of the 270 species of Senecio (Asteraceae) which occurs in Argentina. The structure and absolute configuration of this compound [9a-hydroxy-3,4a,5-trimethyl-4a,6,7,8a,9,9a-hexahydro-4H,5H-naphtho[2,3-b]-furan-2,8-dione or (4S,5R,8R,10S)-1-oxo-8ß-hydroxy-10ßH-eremophil-7(11)-en-12,8ß-olide, C15H20O4] were determined by single-crystal X-ray diffraction studies. It proved to be a sesquiterpene lactone showing an eremophilanolide skeleton whose chirality is described as 4S,5R,8R,10S. Structural results were also in agreement with the one- and two-dimensional (1D and 2D) NMR and HR-ESI-MS data, and other complementary spectroscopic information. In addition, (-)-Istanbulin A is a polymorph of the previously reported form of (-)-Istanbulin A, form I; thus, the title compound is denoted form II or polymorph II. Structural data and a literature search allowed the chirality of Istanbulin A to be revisited. The antimicrobial and antifungal activities of (-)-Istanbulin A, form II, were evaluated in order to establish a reference for future comparisons and applications related to specific crystal forms of Istanbulins.
Assuntos
Antifúngicos/química , Furanos/química , Sesquiterpenos/química , Cristalografia por Raios X , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , EstereoisomerismoRESUMO
The obligate intracellular parasite, Trypanosoma cruzi is the etiologic agent of Chagas disease or American trypanosomiasis, which is the most prevalent parasitic disease in the Americas. The present chemotherapy to control this illness is still deficient particularly in the chronic stage of the disease. The ergosterol biosynthesis pathway has received much attention as a molecular target for the development of new drugs for Chagas disease. Especially, inhibitors of the enzymatic activity of squalene synthase were shown to be effective compounds on T. cruzi proliferation in in vitro assays. In the present study we designed, synthesized and evaluated the effect of a number of isosteric analogues of WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, on T. cruzi growth in tissue culture cells. The selenium-containing derivatives turned out to be extremely potent inhibitors of T. cruzi growth. Certainly, 3-phenoxyphenoxyethyl, 4-phenoxyphenoxyethyl, 4-(3-fluorophenoxy)phenoxyethyl, 3-(3-fluorophenoxy)phenoxyethyl selenocyanates and (±)-5-phenoxy-2-(selenocyanatomethyl)-2,3-dihydrobenzofuran arose as relevant members of this family of compounds, which exhibited effective ED50 values of 0.084⯵M, 0.11⯵M, 0.083,⯵M, 0.085, and 0.075⯵M, respectively. The results indicate that compounds bearing the selenocyanate moiety are at least two orders of magnitude more potent than the corresponding skeleton counterpart bearing the thiocyanate group. Surprisingly, these compounds exhibited excellent selectively index values ranging from 900 to 1800 making these molecules promising candidates as antiparasitic agents.
Assuntos
Éteres Fenílicos/farmacologia , Selênio/farmacologia , Tiocianatos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Éteres Fenílicos/síntese química , Éteres Fenílicos/química , Selênio/química , Relação Estrutura-Atividade , Tiocianatos/síntese química , Tiocianatos/química , Tripanossomicidas/síntese química , Tripanossomicidas/química , Trypanosoma cruzi/citologia , Trypanosoma cruzi/crescimento & desenvolvimento , Células VeroRESUMO
Despite the large number of reported crystalline structures of coordination complexes bearing pyridines as ligands, the relevance of π-π interactions among these hereroaromatic systems in the stabilization of their supramolecular structures and properties is not very well documented in the recent literature. The title compound, [CoCl2(C5H6N2)2], was obtained as bright-blue crystals suitable for single-crystal X-ray diffraction analysis from the reaction of 4-aminopyridine with cobalt(II) chloride in ethanol. The new complex was fully characterized by a variety of spectroscopic techniques and single-crystal X-ray diffraction. The crystal structure showed a tetrahedral complex stabilized mainly by bidimensional motifs constructed by π-π interactions with large horizontal displacements between the 4-aminopyridine units, and N-H...Cl hydrogen bonds. Other short contacts, such as C-H...Cl interactions, complete the three-dimensional arrangement. The supramolecular investigation was extended by statistical studies using the Cambridge Structural Database and a Hirshfeld surface analysis.
RESUMO
Fundamento: la misión de la universidad contemporánea es formar recursos humanos que respondan a las exigencias de la sociedad, por lo que resulta indispensable evaluar continuamente la calidad del proceso docente educativo. Objetivo: diseñar una metodología que permita evaluar el nivel de satisfacción de estudiantes, profesores y directivos que participan directamente en el proceso docente educativo de la disciplina Morfofisiología como indicador de calidad. Métodos: se diseñó una metodología validada por expertos y sustentada en indicadores de calidad, a nivel grupal e individual que incluye cuestionarios de opinión de estudiantes, profesores y directivos así como grupo focal en los que se analizan variables como: la planificación y ejecución del proceso, los aspectos organizativos y funcionales, el clima organizacional, calidad gerencial y trabajo educativo.Resultados: se establece la metodología para la evolución de la satisfacción de los estudiantes, de los docentes y directivos en la ejecución del proceso docente educativo en Morfofisiología como indicador de calidad del mismo, con las unidades de análisis a nivel de grupo e individual. En cada caso se definen indicadores y escala evaluativa de cada uno de ellos. Conclusiones: la metodología diseñada permite evaluar el nivel de satisfacción de estudiantes, profesores y directivos y determinar los factores que repercuten en la calidad del proceso docente educativo de la disciplina Morfofisiología(AU)
Background: the mission of the modern university is to train human resources that meet the demands of society; therefore it is essential to continually assess the quality of the educational process. Objective: to design a methodology to assess the level of satisfaction of students, professors and administrators directly involved in the educational process in the discipline of Morphophysiology as a quality indicator.Methods: a methodology validated by experts and based on quality indicators was designed at group and individual level, including opinion-based questionnaires for students, professors and administrators, as well as focus group. Variables analyzed were: planning and implementation of the process, organizational and functional aspects, organizational climate, managerial quality and educational work. Results: the methodology for assessing the satisfaction of students, professors and administrators with the implementation of the educational process in Morphophysiology as a quality indicator was established, with units of analysis at the group and individual level. In each case, indicators and scale for assessment were defined.Conclusions: the designed methodology allows assessing the level of satisfaction of students, professors and administrators, and determining the factors that affect the quality of the educational process in the discipline of Morphophysiology(AU)
Assuntos
Humanos , Estudos de Avaliação como Assunto , Educação Médica/métodos , Educação Médica/organização & administraçãoRESUMO
Fundamento: la misión de la universidad contemporánea es formar recursos humanos que respondan a las exigencias de la sociedad, por lo que resulta indispensable evaluar continuamente la calidad del proceso docente educativo que se suscita hoy en estos centros docentes. Objetivo: evaluar el nivel de satisfacción de estudiantes, profesores y directivos que participan directamente en el proceso docente educativo en la disciplina Morfofisiología. Métodos: se aplica una metodología validada por expertos y compuesta por indicadores de calidad, a nivel grupal e individual que incluye la aplicación de cuestionarios de opinión a estudiantes, profesores y directivos así como grupo focal en los que se analizan variables como: la planificación yejecución del proceso, los aspectos organizativos y funcionales, el clima organizacional, la calidad gerencial y el trabajo educativo. Resultados: los indicadores que más afectan el nivel de satisfacción en el caso de los estudiantes y profesores fueron: la calidad de las conferencias orientadoras y el acceso a las tecnologías; en cuanto a los directivos: el insuficiente control y asesoría por los especialistas y metodólogos de la facultad al proceso docente-educativo. Conclusión: la metodología aplicada permite evaluar el nivel de satisfacción de estudiantes, profesores y directivos y determinar los factores que comprometen la calidad del proceso docente- educativo de la disciplina Morfofisiología(AU)
Background: to improve the quality of the educational process in Morphophysiology. Objective: to assess the satisfaction level of students, teachers and managers directly involved in the educational process inMorphophysiology. Methods: a methodology validated by experts and supported by quality indicators atindividual and group level is applied. It includes surveys for students, teachers and managers and focus group forthe analysis of variables such as planning and execution of the process, organizational and functional aspects,organizational environment, management quality and educational work. Results: the indicators that affect the satisfaction level of students and teachers are the quality of lectures and the access to technologies. As formanagers, it is the lack of control and advice by specialists and methodologists of the educationalprocess in the faculty. Conclusion: the methodology used allows assessing the satisfaction level of students, teachers and managers as well as determining thefactors that affect the quality of the educational process in Morphophysiolog(AU)