Novel substituted quinazolines for potent EGFR tyrosine kinase inhibitors.

The type I receptor tyrosine kinases (RTKs) are involved in various aspects of cell growth, survival, and differentiation. Among the known RTKs, the epidermal growth factor receptor (EGFR) and ErbB-2 (HER-2) are two widely studied proteins that are prototypic members of the ErbB family which also includes ErbB-3 (Her-3) and ErbB-4 (Her-4). Overexpression of ErbB-2 and EGFR has been associated with aggressive disease and poor patient prognosis in a range of human tumour types (e.g. breast, lung, ovarian, prostate, and squamous carcinoma of head and neck). Disruption of signal transduction of these kinases has been shown to have an antiproliferative effect. Various approaches have been developed to target the ErbB signalling pathways including monoclonal antibodies (trastuzumab/Herceptin™ and cetuximab/Erbitux™) directed against the receptor, and synthetic tyrosine kinase inhibitors (gefitinib/Iressa™ and erlotinib/Tarceva™). Since many tumours overexpress ErbB receptors, simultaneous targeting of multiple ErbB receptors therefore becomes a promising approach to cancer treatment. Lapatinib (Tykerb™), a potent dual EGFR/ErbB-2 inhibitor, was approved for the treatment of ErbB-2-positive breast cancer. Despite years of intensive research on EGFR inhibitors, there is a surprising dearth of chemically distinct small inhibitors with a high degree of selectivity. There is also a need for new scaffolds due to the recent finding of EGFR mutations which render the kinase resistant to gefinitib and erlotinib. The structures under study will be quinazolines with different substituents. The structure-activity relationships and biological evaluation of compounds published during the last four years will be reviewed herein.

Uso de una aplicación web – SciFinder - como complemento para el desarrollo de la asignatura de Química Orgánica en la Licenciatura de Farmacia / The use of a web application – SciFinder to complement the Organic Chemistry teaching to the student of the Degree in Pharmacy

La necesidad de motivación del alumno, además de la adaptación de la actual enseñanza a los créditosECTS, han sido los motores que nos han llevado a proponer el uso de una aplicación web denominadaSciFinder en la enseñanza de la Química Orgánica. Se trata de una herramienta imprescindible en lainvestigación avanzada que se utiliza en cualquier laboratorio de síntesis química.La Universidad de Granada dispone de una suscripción que permite 6 usos simultáneos a la que elalumno puede acceder a través de un acceso directo a SciFinder on Web en el sólo es necesarioregistrarse como usuario.Permitir al alumno transportarse a un laboratorio virtual es una de las múltiples posibilidades queofrece esta aplicación web ayudándoles a complementar los conocimientos científicos básicos que sehan explicado en clase.Durante el desarrollo de los distintos temas que componen la asignatura se plantearán reaccionesconcretas que el alumno deberá ampliar con la información que esta aplicación les proporciona:reactivos empleados en dichas reaccionescondiciones de reacción (estequiometría, tiempo, temperatura…)bibliografía actual.Al final del curso académico se evaluará esta nueva experiencia mediante encuestas de opinión delalumnado para determinar dos aspectos fundamentales de la misma, el aumento de interés por laasignatura durante el desarrollo del trabajo y la dificultad en la realización del mismo(AU)

The need to motivate the students, besides adapting the teaching to the ECTS credits, have been thedriving force that leads us to propose the use of a web application called Sci Finder in the education ofOrganic Chemistry. It is an essential tool used in any advanced research laboratory of syntheticchemistry.The University of Granada provides a subscription with 6 simultaneous accesses. The students mayaccede directly to the SciFinder on Web being only necessary the registration as users.One of the many possibilities that offers this web application allows to the student be transported to avirtual laboratory and complement the basic scientific knowledge explained in class.During the development of the different topics, specific reactions will be presented to the student andthey may increase the information by using this application:reagents of the reactionsreaction conditions (stoichiometry, time, temperature…)up-to-date bibliographyAt the end of the academic year this new experience will be evaluate through opinion poll to thestudent in order to determinate two essential aspect, the interest increase for the subject during thedevelopment of this work and the difficulty in carrying out it(AU)

[A case of visceral leishmaniasis]. / Un caso de Leishmaniasis visceral.

A case of leishmaniasis (L. donovani) in a five year-old girl from Acatlan, State of Puebla, Mexico, is reported. She had had a 4-month history of malaise with 39 degrees C intermittent fever, hyporexia and a weight loss of 7 kg. She had spleen enlargement, and blood pancytopenia. A bone marrow study showed the Leishmania amastigotes; a positive blood culture on NNN media (Novy-Nicolle-MacNeal) confirmed the presence of promastigotes. A complete remission was achieved with methylglucamine. We present a review of the Mexican literature concerning visceral leishmaniasis.