Síntese e avaliação de novos análogos do Canabidiol com efeitos neuroprotetores contra a Doença de Alzheimer

Abstract

Cannabidiol (CBD) is an abundant phytocannabinoid in Cannabis sativa, with no psychotropic effects, that has been intensively studied in recent decades for its biological and medicinal properties. As a result, numerous studies have highlighted its possible therapeutic applications, such as the treatment of cancer, pain, chronic inflammation, neurodegenerative diseases (NDs), epilepsy, depression, and anxiety. Thus, research into NDs, such as Alzheimer's disease (AD) and Parkinson's disease (PD), is gaining a new approach, aimed at symptomatic treatment and finding novel compounds that act by reversing or reducing the characteristic neuroinflammatory condition of these neuropathologies. In this context, this work aimed at the synthesis, characterization, and pharmacological evaluation of new structural analogs of CBD, obtained from R- and S-carvones, seeking to identify their antioxidant, neuroprotective, and cholinesterase inhibitory activities, to identify multifunctional ligands with useful properties for the treatment of NDs, especially AD. As a result, fifty compounds, with novel molecular structures were synthesized. These compounds belong to three different series, namely carvonoyl-cinamoyl-N-acyl-hydrazones CCNA, 26 compounds), oxime-benzamides (OB, 12 compounds), and oxime-cinnamoyl amides (OC, 12 compounds). Among these, 19 compounds were BuChE inhibitors, 13 substances stood out as neuroprotectors, 12 compounds exhibited free radical scavenging activity, and 4 presented a multitarget profile.