Gisela C. Muscia

Synthesis, trypanocidal activity and molecular modeling studies of 2-alkylaminomethylquinoline derivatives

Research and development of new drugs effective in the treatment of Trypanosoma cruzi infections are a real need for the 16 million people infected in the Americas. In a previous work, a quinoline derivative substituted by a 2-piperidylmethyl moiety showed to be active against Chagas disease and was considered a lead compound for further optimization. A series of ten analogous derivatives were tested against epimastigotes as a first approach. In view of their promising results, six of them were evaluated against the blood and intracellular replicative forms of the parasite in humans. Among them, compound 12 which possesses a 6-acetamidohexylamino substituent showed remarkable improvement in activity against epimastigotes, trypomastigotes and amastigotes compared with the structure lead, as well as a good selectivity index for the two parasite stages present in humans. In addition, treatment of infected mice with compound 12 induced a significant reduction in parasitemia compared with non-treated mice. Molecular modeling studies were performed by computational methods in order to elucidate the factors determining these experimental bioactivities.

EVALUATION OF ANTIPARASITIC, ANTITUBERCULOSIS AND ANTIANGIOGENIC ACTIVITIES OF 3-AMINOQUINOLIN-2-ONE DERIVATIVES

Parasitic infections such as leishmaniasis, trypanosomiasis and malaria have significant impacts in third world countries and are the major reasons of mortality. In order to search a new class of antiprotozoal agent, a series of ten quinolin-2-one derivatives was tested in vitro against the parasites causative of malaria, leishmaniasis, sleeping sickness and Chagas´ disease. In general, these compounds exhibited moderate activity against Plasmodium falciparum and showed no activity against Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Facing to establish a possible mechanism of antimalarial activity their binding to hemin was assayed. Furthermore, the need of developing new therapeutic strategies for the effective control of tuberculosis prompted us to assay twelve of these compounds against Mycobacterium tuberculosis but they did not demonstrate inhibitory activity. In addition, three terms resulted also structurally related to linomide, a recognized drug against angiogenesis, an interesting target for designing new antineoplastic agents. So these compounds were selected at the National Cancer Institute for angiogenesis testing and they exhibited similar activity to those recently reported for linomide and its analogues

Synthesis and evaluation of 2-(1H-indol-3-yl)-4-phenylquinolines as inhibitors of cholesterol esterase.

A series of 2-(substituted) phenyl and 2-indolyl quinoline derivatives (10a-l) was synthesized by an efficient microwave-assisted, trifluoroacetic acid-catalyzed, solvent-free method. Evaluation of the inhibitory activity led to the identification of two quinoline inhibitors of cholesterol esterase. 2-(1H-Indol-3-yl)-6-nitro-4-phenylquinoline (10l; IC50=1.98μM) was characterized as a mixed-type inhibitor with a pronounced competitive binding mode.

Una fundamentación para la incorporación de la química verde en los currículos de química orgánica

ABSTRACT ( Foundations for Considering Green Chemistry in Organic Chemistry Curriculum) Green Chemistry proposes the design of products and processes that reduce or eliminate the use or generation of hazardous substances. This new philosophy seeks to train the next generation of scien-tists in the methodologies, techniques and principles that are central to the area. The Green Chemistry must be involved into the curriculo as an integral part of the chemistry courses of the Pharmacy and Biochemistry careers, at the University of Buenos Aires. In order to determine whether students have knowledge about Sustainable Chemistry they were questioned, with appropriate inquiries, on the tar-get discipline. Almost all students are not related with the Green Chemistry principles; thus, taking into account the obtained results it must be highlighted the necessity to lead into the Green Chemistry Protocol in the curricula of common chemistry courses. The introduction in the curriculo of concepts related to the discipline is made possible since small changes could be made in the practical work. As a specific example referred to the oxidation of cyclohexanol to cyclohexanone using a methodology and reagents that present multiple advantages compared to traditional technique.

Campus Virtual y Facebook en el ámbito universitario. ¿Enemigos o aliados en los procesos de enseñanza y aprendizaje?

Virtual Campus and Facebook in the university. Enemies or Allies in the teaching and learning processes? Our students live in a new era of communication. For many years chemists have used technology for teaching and learning at different levels of education. The use of virtual platforms is a valuable educational tool. The aim of this paper is to analyze the use of virtual platforms for students enrolled in the Organic Chemistry II course, of the careers of Pharmacy and Biochemistry, University of Buenos Aires. We have compared the use of the Virtual Campus and Facebook groups. A sample of 110 randomly selected students participated in this research. The 100% of students were registered on the campus of Organic Chemistry II and the 80% was a member of a related Facebook group. The 90% of the students used some of these technological tools as a means to support their questions. Moreover, 67% of respondents prefer Facebook as a means of communication. The 64% of students felt that Facebook was the means by which they obtained a rapid response. TheVirtual Campus and Facebook in the university. Enemies or Allies in the teaching and learning processes?) Our students live in a new era of communication. For many years chemists have used technology for teaching and learning at different levels of education. The use of virtual platforms is a valuable educational tool. The aim of this paper is to analyze the use of virtual platforms for students enrolled in the Organic Chemistry II course, of the careers of Pharmacy and Biochemistry, University of Buenos Aires. We have compared the use of the Virtual Campus and Facebook groups. A sample of 110 randomly selected students participated in this research. The 100% of students were registered on the campus of Organic Chemistry II and the 80% was a member of a related Facebook group. The 90% of the students used some of these technological tools as a means to support their questions. Moreover, 67% of respondents prefer Facebook as a means of communication. The 64% of students felt that Facebook was the means by which they obtained a rapid response. The results indicate that students use virtual platforms as a support tool in the learning process.

Utilización de tecnología multimedia para la enseñanza de estereoquímica en el ámbito universitario

En la ensenanza de la quimica, el mayor inconveniente es que los atomos y las moleculas son estructuras muy pequenas a las cuales no tenemos posibilidad de observar. Por lo tanto, nos valemos de un modelo mental que sea valido para la ensenanza de esta ciencia. El objetivo de este trabajo es la implemen¬tacion del ChemBio3DUltra v11.0 para generar representaciones tridimensionales y contribuir a elevar la calidad del proceso de ensenanza en relacion a la ensenanza tradicional. Una muestra de 200 estudiantes inscriptos en la asignatura Quimica Organica II, del plan de estudios de las carreras de Farmacia y Bioquimica de la Universidad de Buenos Aires, participaron en la investigacion. El grupo de estudio fue conformado por 100 alumnos y el grupo control por otros 100 estudiantes. Los alumnos fueron indagados sobre la utilidad del programa en el desarrollo del topico Estereoquimica. Nosotros analizamos su desempeno en la instancia evaluativa. En nuestro caso observamos que el uso del ChemBioUltra v11.0 resulto de utilidad para los alumnos. En la instancia evaluativa, aproximadamente, un 50% mas de alumnos obtuvieron la mayor puntuacion en comparacion con la muestra control.

Microwave-assisted Synthesis of 2-Styrylquinoline-4-carboxylic Acids as Antitubercular Agents

BACKGROUND Many 2-substituted quinolines and especially 2-arylvinyl derivatives isolated from plants or prepared by synthesis have been designed from ethnopharmacological studies. OBJECTIVE In order to explore new aspects of the structure-antituberculosis activity relationship, a series of styrylquinoline derivatives was prepared. METHOD A series of styrylquinoline derivatives was prepared from quinaldic acid and a variety of arylbenzaldehydes under eco-friendly conditions via Knoevenagel reaction and trifluoroacetic acid (TFA) as catalyst. RESULTS The products were obtained in short reaction times and good yields and were evaluated for growth inhibitory activity towards Mycobacterium tuberculosis H37Rv (Mtb) through the National Institute of Allergy and Infectious Diseases (NIAID, USA). CONCLUSION Three compounds had activity under aerobic conditions.