Recent Development of Hybrids and Derivatives of Resveratrol in Neurodegenerative Diseases

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Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons in different regions of the nervous system, being Alzheimer’s disease (AD) and Parkinson’s disease (PD) the most common NDs. Despite their high incidence, the pharmacological treatments are mainly symptomatic. For this reason, in recent years, the research has been focused on the discovery of new molecules able to target neuropathological pathways involved in NDs. In the last decades, several researchers investigated the neuroprotective actions of naturally occurring polyphenols, such as resveratrol, that has attracted special interest since its ability to interact simultaneously with the multiple targets implicated in NDs. Thanks to the structural simplicity of the stilbene core, the broad spectrum of possible modifications, and the improved synthetic strategies, resveratrol is an attractive chemical starting point for the searching of new entities with extended therapeutic uses in NDs. In this review, a systematic update of the stilbene-based hybrids and derivatives, and SAR analysis were provided for the development of new drugs potentially useful as NDs multitarget directed ligands.