Melatonin-and resveratrol-based multitarget-directed agents for Alzheimer's disease and photoswitchable muscular nicotinic receptor ligands

Abstract

Alzheimer´s disease (AD) is a complex multifactorial illness with no effective treatment, characterized by irreversible global cognitive impairment. As only symptomatic treatment sare available with drugs acting at one single target, exploration of molecules active indifferent pathological targets is required. In this chapter, our objective was to develop new families of multitarget directed ligands (MTDLs) focused on some pathological pathways underlying AD, namely, oxidative stress and neuro inflammation. Thus, we design melatonin- and resveratrol-based MTDLs looking for activity in melatonin receptors (MT1-3Rs), monoaminoxidases (MAO-A/B), lipoxygenase-5 (LOX-5), and nuclear factor erythroid 2-related factor 2 (Nrf2). Considering the neuroprotective and neurogenic properties found in melatonin and resveratrol, we reasonably expected these activities in our MTDLs...La enfermedad de Alzheimer (EA) es un desorden multifactorial sin cura efectiva,caracterizada por un deterioro cognitivo global. Los tratamientos disponibles son sólo sintomáticos con fármacos que actúan sobre una sola diana, siendo necesarias moléculas activas por diferentes vías. En este capítulo, nuestro objetivo es desarrollar nuevas familias de ligandos multidiana (MTDL) enfocados hacia vías patológicas de la EA, concretamente, el estrés oxidativo y neuroinflamación. Así, desarrollamos MTDLs basados en melatoninay resveratrol buscando actividad en receptores de melatonina (MT1-3Rs), monoaminooxidasas (MAO-A/B), lipoxigenasa-5 (LOX-5) y el factor nuclear (erythroid-derived 2)-like 2 (Nrf2). Considerando las propiedades neuroprotectoras y neurogénicas de la melatonina y el resveratrol, esperamos razonablemente estas actividades en nuestros MTDLs...