Biomimetic synthesis of rare cannabigerol-type cannabinoids and evaluation of their cytotoxic effect on human glioblastoma cell lines

Although Cannabis sativa L. is well known for being prolific in phytocannabinoids, their biosynthetic modular mechanism is ruled by a main enzyme: the geranyltransferase able to pursue the C-isoprenylation of olivetolic acid with the geranyldiphosphate. However, the existence of more than 160 meroterpenoids can be partially explained by a side degree of promiscuity of the geranyltransferase itself, able to recognise different substrate than the ordinary ones. This biological process led to the identification of several unconventional phytocannabinoids with a limited distribution in the plant both for occurrence and concentration. Taking advance of the existing synthetic protocols and using as example the enzymatic promiscuity, we propose a bio-inspired synthesis of naturally occurring minor cannabinoids related to the cannabigerol-type and their preliminary biological inspection in U87, U251 and T98 human glioblastoma cell lines to investigate their potential contribute as supplement in anticancer therapy.