title: Dibenzocyclooctadiene lignans from Schisandra spp. selectively inhibit the growth of the intracellular bacteria Chlamydia pneumoniae and Chlamydia trachomatis.
abstract: Lignans from Schisandra chinensis berries show various pharmacological activities, of which their antioxidative and cytoprotective properties are among the most studied ones. Here, the first report on antibacterial properties of six dibenzocyclooctadiene lignans found in Schisandra spp. is presented. The activity was shown on two related intracellular Gram-negative bacteria Chlamydia pneumoniae and Chlamydia trachomatis upon their infection in human epithelial cells. All six lignans inhibited C. pneumoniae inclusion formation and infectious progeny production. Schisandrin B inhibited C. pneumoniae inclusion formation even when administered 8 h post infection, indicating a target that occurs relatively late within the infection cycle. Upon infection, lignan-pretreated C. pneumoniae elementary bodies had impaired inclusion formation capacity. The presence and substitution pattern of methylenedioxy, methoxy and hydroxyl groups of the lignans had a profound impact on the antichlamydial activity. In addition our data suggest that the antichlamydial activity is not caused only by the antioxidative properties of the lignans. None of the compounds showed inhibition on seven other bacteria, suggesting a degree of selectivity of the antibacterial effect. Taken together, the data presented support a role of the studied lignans as interesting antichlamydial lead compounds.
authors.affiliation: Pharmaceutical Biology, CDR, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Hakala
authors.affiliation: Pharmaceutical Biology, CDR, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Hanski
authors.affiliation: Laboratories for Chemical Biology Umeå, Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Uvell
authors.affiliation: Pharmaceutical Biology, CDR, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Teijo
authors.initials: T
authors.lastname: Yrjönen
authors.affiliation: Pharmaceutical Biology, CDR, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Vuorela
authors.affiliation: Laboratories for Chemical Biology Umeå, Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Elofsson
authors.affiliation: Pharmaceutical Biology, CDR, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Pia Maarit
authors.initials: PM
authors.lastname: Vuorela
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D002460:Cell Line; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development* / Q000472:pathogenicity; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000254:growth & development* / Q000472:pathogenicity; D034242:Cyclooctanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011083:Polycyclic Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C510994:dibenzocyclooctadiene lignan; C015499:schizandrin B; C034734:schizandrin A