PRIN_VITALE_2017WN73PL-004_Bioactivity-directed exploration of the phytocannabinoid chemical space (DCM.AD007.100)
Area progettualeChimica e materiali per la salute e le scienze della vita (DCM.AD007)
Struttura responsabile del progetto di ricerca
Responsabile di progetto
Phytocannabinoids, a class of over 200 meroterpenoids, show a surprising diversity of macromolecule targets and qualify as privileged structure for biomedical research. However, their chemical and biological space has so far been systematically investigated only around the so-called "big 4", that is, the major non-native (decarboxylated) constituents of the plant (delta9-THC, CBD, CBG and CBD), and mostly in the context of a single end-point (CB1). Capitalizing on the increased availability of cannabinoids by isolation (strain selection, advances in separation techniques) and synthesis, the chemical and biological space around the native forms of phytocannabinoids and a selection of minor analogues representative of the biosynthetic exuberance of Cannabis will be systematically explored, focusing on targets of relevance for the non-narcotic modulation of the endocannabinoid system and the identification of novel end-points. Based on these results, environmental issues associated to the increased human exposure to phytocannabinoids secondary to changes in Cannabis legislation will be investigated.
The results of this Project are expected to contribute not only to the advancement of chemical and biomedical research, but also to the socially divisive ongoing Cannabis debate. They are summarized in Project Deliverables:
o Exploration of the dark area of the cannabinome: Stable pro-drugs of pre-cannabinoids and library of minor phytocannabinoids and analogues.
o Environmental issues associated to the increased human exposure to phytocannabinoids: Behavioral effects of phytocannabinoids and their major human metabolites in a zebrafish model.
To identify in the natural cannabinome, or to discover by means of its synthetic or semi-synthetic elaboration, new candidates for further preclinical development in some of the clinical areas where malfunctioning of the endocannabinoid system is involved or its manipulation could be beneficial: i.e. chronic neurodegenerative diseases like multiple sclerosis and Alzheimer's disease, and the management of acute and chronic pain. Finally, to provide information on the potential effects on fish life and behavior of the presence of phytocannabinoids and their metabolites in waste water, an issue of growing ecological concern.
Data inizio attività
CHEMISTRY, MEDICINAL, RECEPTOR
Ultimo aggiornamento: 06/12/2023