Defensa de tesis doctoral en el Instituto Teófilo Hernando
31 DE OCTUBRE A LAS 12.00H EN LA PAGODA
El próximo 31 de octubre de 2019 (12.00 horas, edificio La Pagoda, Facultad de Medicina UAM) defenderá su tesis la doctoranda del Instituto Teófilo Hernando de I+D del Medicamento de la Universidad Autónoma de Madrid, Sheila Abril Comesaña.
Conozca el trabajo defendido:
Título: “Novel multitarget chiral α7-nAChRs ligands with neuroprotective properties for Alzheimer’s Disease treatment”.
Directores: Dr. Rafael León Martínez y Dra. Mercedes Salaices.
Resumen de la tesis:
Alzheimer’s Disease, a multifactorial disease and the most common form of dementia, still has not efficacious treatment despite the utmost efforts of the scientific community. Therefore, the development of novel drugs able to stop the disease progression is an urgent socio-economic necessity. In this regard, this Doctoral Thesis is centred on the rational design, synthesis and pharmacological evaluation of novel molecules belonging to the new class of multitarget directed ligands. Two new families of chiral compounds were obtained: Family A derivatives were simultaneously NRF2 inducers, selective α7-nAChRs ligands, free radical scavengers, AChE inhibitors and neuroprotectant agents.
Nevertheless, the brain distribution studies demonstrated that they were actively effluxed from the brain, suggesting a low distribution in our regions of interest. These results led us to design a second generation of molecules with improved physicochemical properties. Thus, Family B compounds possessed a potent free radical scavenger capacity and a selective α7-nAChRs agonism, whose combination promoted a promising neuroprotective effect. These novel molecules were conceived to act synergistically on different pathological events of the neurodegenerative process in order to prevent Alzheimer’s Disease progression.