title: Phytocannabinoids: a unified critical inventory.
abstract: Covering up to January 2016Cannabis sativa L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl- and a β-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi). The startling diversity of cannabis phytocannabinoids might be, at least in part, the result of non-enzymatic transformations induced by heat, light, and atmospheric oxygen on a limited set of major constituents (CBG, CBD, Δ9-THC and CBC and their corresponding acidic versions), whose degradation is detailed to emphasize this possibility. The diversity of metabotropic (cannabinoid receptors), ionotropic (thermos-TRPs), and transcription factors (PPARs) targeted by phytocannabinoids is discussed. The integrated inventory of these compounds and their biological macromolecular end-points highlights the opportunities that phytocannabinoids offer to access desirable drug-like space beyond the one associated to the narcotic target CB1.
authors.affiliation: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University, Ein Kerem Campus, Jerusalem 91120, Israel. lumirh@ekmd.huji.ac.il.
authors.forename: Lumír Ondřej
authors.initials: LO
authors.lastname: Hanuš
authors.affiliation: Phytoplant Research S. L, Rabanales 21 - The Science and Technology Park of Cordoba, 14014, Cordoba, Spain.
authors.forename: Stefan Martin
authors.initials: SM
authors.lastname: Meyer
authors.affiliation: Maimonides Biomedical Research Institute of Córdoba, Reina Sofía University Hospital, Department of Cell Biology, Physiology and Immunology, University of Córdoba, Avda Menéndez Pidal s/n., 14004, Córdoba, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via Montesano 49, 80131 Napoli, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Taglialatela-Scafati
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy. giovanni.appendino@uniupo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Appendino
mesh_terms: D002186:Cannabinoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002188:Cannabis / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D002186:Cannabinoids