title: Secondary metabolites from cetrarioid lichens: Chemotaxonomy, biological activities and pharmaceutical potential.
abstract: BACKGROUND
  Lichens, as a symbiotic association of photobionts and mycobionts, display an unmatched environmental adaptability and a great chemical diversity. As an important morphological group, cetrarioid lichens are one of the most studied lichen taxa for their phylogeny, secondary chemistry, bioactivities and uses in folk medicines, especially the lichen Cetraria islandica. However, insufficient structure elucidation and discrepancy in bioactivity results could be found in a few studies.
  
  
  OBJECTIVE
  This review aimed to present a more detailed and updated overview of the knowledge of secondary metabolites from cetrarioid lichens in a critical manner, highlighting their potentials for pharmaceuticals as well as other applications. Here we also highlight the uses of molecular phylogenetics, metabolomics and ChemGPS-NP model for future bioprospecting, taxonomy and drug screening to accelerate applications of those lichen substances.
  The paper starts with a short introduction in to the studies of lichen secondary metabolites, the biological classification of cetrarioid lichens and the aim. In light of ethnic uses of cetrarioid lichens for therapeutic purposes, molecular phylogeny is proposed as a tool for future bioprospecting of cetrarioid lichens, followed by a brief discussion of the taxonomic value of lichen substances. Then a delicate description of the bioactivities, patents, updated chemical structures and lichen sources is presented, where lichen substances are grouped by their chemical structures and discussed about their bioactivity in comparison with reference compounds. To accelerate the discovery of bioactivities and potential drug targets of lichen substances, the application of the ChemGPS NP model is highlighted. Finally the safety concerns of lichen substances (i.e. toxicity and immunogenicity) and future-prospects in the field are exhibited.
  
  
  CONCLUSIONS
  While the ethnic uses of cetrarioid lichens and the pharmaceutical potential of their secondary metabolites have been recognized, the knowledge of a large number of lichen substances with interesting structures is still limited to various in vitro assays with insufficient biological annotations, and this area still deserves more research in bioactivity, drug targets and screening. Attention should be paid on the accurate interpretation of their bioactivity for further applications avoiding over-interpretations from various in vitro bioassays.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Maonian
authors.initials: M
authors.lastname: Xu
authors.affiliation: Icelandic Institute of Natural History, Akureyri Division, IS-600 Akureyri, Iceland.
authors.forename: Starri
authors.initials: S
authors.lastname: Heidmarsson
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Elin Soffia
authors.initials: ES
authors.lastname: Olafsdottir
authors.affiliation: Chemistry Innovation Centre, Discovery Sciences, AstraZeneca R&D Mölndal, Pepparedsleden 1, Mölndal SE-43183, Sweden.
authors.forename: Rosa
authors.initials: R
authors.lastname: Buonfiglio
authors.affiliation: Chemistry Innovation Centre, Discovery Sciences, AstraZeneca R&D Mölndal, Pepparedsleden 1, Mölndal SE-43183, Sweden.
authors.forename: Thierry
authors.initials: T
authors.lastname: Kogej
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. Electronic address: sesselo@hi.is.
authors.forename: Sesselja
authors.initials: S
authors.lastname: Omarsdottir
mesh_terms: D065132:Bioprospecting; D008011:Lichens / Q000737:chemistry* / Q000145:classification; D015394:Molecular Structure; D010802:Phylogeny; D064210:Secondary Metabolism
keywords: Cetrarioid lichens; Chemotaxonomy; Ethnopharmacology; Lichen substances; Pharmaceutical potential; Phylogeny