Curcumin, Resveratrol and Cannabidiol as natural key-prototypes in drug design for neuroprotective agents

Nowadays, neurodegenerative diseases (NDs), such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge for different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology, and medicine, once all these pathologies remain incurable, with high socio-economic impacts and high costs for governmental health services. Due to their severity and multifactorial pathophysiological complexity, the available approved drugs for clinics have not yet shown adequate effectiveness in disease-modifying effects, with very restricting options in the therapeutic arsenal, which highlight the permanent need for continued drug discovery efforts in Academia and Industry. In this context, natural products, such as curcumin (1), resveratrol (2), and cannabidiol (CBD, 3) have been recognized as important sources of inspiration, promising chemical entities, prototype models, and starting materials for medicinal organic chemistry. Once their molecular architecture, multifunctional properties and single chemical diversity could address the discovery, optimization, and development of innovative drug candidates with improved pharmacodynamics and pharmacokinetics compared to the known drugs, there may be a real chance of discovering novel effective drugs to combat NDs. In this review, we report the most recent efforts of medicinal chemists worldwide, published in the scientific literature available in PubMed, SCOPUS, and Web of Sciences database, during the last 10 years of research devoted to the exploration of curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) as starting materials or privileged scaffolds in the design of multi-target directed ligands (MTDLs) with potential therapeutic properties against NDs.