Sulfamidas: aspectos farmacológicos y químico – terapéuticos

Las sulfamidas son antibióticos bacteriostáticos muy selectivos y seguros, ya que actúan mediante el bloqueo de la dihidropteroato sintasa, enzima exclusivamente bacteriana. Esta inhibición impide la síntesis de ácido fólico, cofactor imprescindible para la obtención de bases nitrogenadas, y por tanto de ADN bacteriano, bloqueando la proliferación del microorganismo. Sin embargo, en las últimas décadas, debido al desarrollo de múltiples tipos de resistencia por parte de los microoganismos, la aparición de algunos efectos adversos importantes y al desarrollo de nuevos fármacos más seguros y eficaces su uso se ha reducido vertiginosamente. Esto ha restringido la utilidad de estos fármacos a casos muy concretos como la profilaxis de la transmisión vertical en malaria, toxoplasmosis o al tratamiento de algunas infecciones cutáneas. A pesar de este hecho, en el Grado en Farmacia se sigue estudiando la síntesis de estos compuestos, ya que es considerada de importante interés académico, por ello tratamos de desarrollar una ruta sintética optimizada y adecuada a las características de un laboratorio de prácticas

Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation

The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin

Aprendizaje de las prácticas de laboratorio de Química Farmacéutica del Grado en Farmacia y Doble Grado en Farmacia y Nutrición a través del aula virtual

Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaFALSEsubmitte

Publicación en acceso abierto en las universidades andaluzas

Elaborado por el Grupo de Trabajo de Apoyo a la Investigación del CBU

Desarrollo de una aplicación informática para dispositivos móviles para la mejora del aprendizaje de la nomenclatura de compuestos orgánicos y de fármacos

Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaFALSEsubmitte

Evaluación de TuFormulas. Diseño y aplicación de indicadores para medir el impacto y la sostenibilidad de este recurso educativo como herramienta de enseñanza y aprendizaje

Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaFALSEsubmitte

Compuestos multidiana derivados de inhibidores de la RHO-Quinasa(Rock) con potencial actividad frente a enfermedades neurodegenerativas

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 18-05-2022Los avances en la terapéutica han aumentado considerablemente la esperanza de vida y, por tanto, la proporción de población anciana, lo que conlleva la aparición de nuevas patologías que se dan en edades avanzadas, como es el caso de las enfermedades neurodegenerativas. La enfermedad de Alzheimer, la de Parkinson o la esclerosis lateral amiotrófica (ELA) son algunos ejemplos de este tipo de enfermedades, cuya relevancia se basa en su prevalencia dentro de este grupo de población, y en la ausencia de un tratamiento curativo o realmente efectivo. Este tipo de enfermedades suelen tener en común una etiología múltiple y complicada, ya que tienden a ser patologías que incluyen alteraciones en varios procesos fisiológicos, normalmente asociadas al envejecimiento. Esta compleja red de alteraciones hace que el desarrollo de fármacos basados en la estrategia clásica de “un fármaco-una diana” no haya logrado una terapia plenamente funcional. Frente a este problema ha surgido una nueva estrategia, la estrategia de fármacos dirigidos a varias dianas, o fármacos multidiana, que contempla que una única entidad química sea capaz de interactuar con varias dianas, de modo que el efecto terapéutico se dé a través de varias vías complementarias, de forma sinérgica...The new advances in therapeutics have increased life expectancy, and therefore the percentage of elder people, leading to an increase in age-related pathologies such as neurodegenerative disorders. Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis (ALS) are some examples of these disorders, which are particularly relevant in drug discovery due to the absence of effective treatments.These age-related disorders have multiple and complex etiologies, since several physiological processes are altered at the same time, leading to a complex network of disturbances. In this scenario, the classical “one drug-one target” approach to drug discovery is not suitable to achieve an efficient therapy. The new approach of multiple target-directed ligands, which proposes that one chemical entity might be able to interact with several targets in a synergistic fashion, seems more promising...Fac. de FarmaciaTRUEunpu

Curcumin-Piperlongumine Hybrids with a Multitarget Profile Elicit Neuroprotection in In Vitro Models of Oxidative Stress and Hyperphosphorylation

Curcumin shows a broad spectrum of activities of relevance in the treatment of Alzheimer’s disease (AD); however, it is poorly absorbed and is also chemically and metabolically unstable, leading to a very low oral bioavailability. A small library of hybrid compounds designed as curcumin analogues and incorporating the key structural fragment of piperlongumine, a natural neuroinflammation inhibitor, were synthesized by a two-step route that combines a three-component reaction between primary amines, β-ketoesters and α-haloesters and a base-promoted acylation with cinnamoyl chlorides. These compounds were predicted to have good oral absorption and CNS permeation, had good scavenging properties in the in vitro DPPH experiment and in a cellular assay based on the oxidation of dichlorofluorescin to a fluorescent species. The compounds showed low toxicity in two cellular models, were potent inductors of the Nrf2-ARE phase II antioxidant response, inhibited PHF6 peptide aggregation, closely related to Tau protein aggregation and were active against the LPS-induced inflammatory response. They also afforded neuroprotection against an oxidative insult induced by inhibition of the mitochondrial respiratory chain with the rotenone-oligomycin A combination and against Tau hyperphosphorylation induced by the phosphatase inhibitor okadaic acid. This multitarget pharmacological profile is highly promising in the development of treatments for AD and provides a good hit structure for future optimization efforts