title: Bioactive cembrane derivatives from the Indian Ocean soft coral, Sinularia kavarattiensis.
abstract: Marine organisms and their metabolites represent a unique source of potential pharmaceutical substances. In this study, we examined marine-derived substances for their bioactive properties in a cell-based Chikungunya virus (CHIKV) replicon model and for in vitro anti-inflammatory activity. In the screening of a marine sample library, crude extracts from the Indian soft coral, Sinularia kavarattiensis, showed promising activity against the CHIKV replicon. Bioassay-guided chemical fractionation of S. kavarattiensis resulted in the isolation of six known norcembranoids (1-6) and one new compound, named kavaranolide (7). The structures were elucidated on the basis of NMR and MS spectroscopic data. Compounds 1-3 and 5-7 were evaluated for their replicon-inhibiting potential in the CHIKV model by using a luminescence-based detection technique and live cell imaging. Compounds 1 and 2 showed moderate inhibition of the CHIKV replicon, but imaging studies also revealed cytotoxic properties. Moreover, the effects of the isolated compounds on primary microglial cells, an experimental model for neuroinflammation, were evaluated. Compound 2 was shown to modulate the immune response in microglial cells and to possess potential anti-inflammatory properties by dose-dependently reducing the release of pro- and anti-inflammatory cytokines.
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, P.O. Box 56, University of Helsinki, Helsinki FI-00014, Finland. katja-emilia.lillsunde@helsinki.fi.
authors: Katja-Emilia
authors: KE
authors: Lillsunde
authors: Department of Pharmacy, University of Naples Federico II (USNF), Naples I-80131, Italy. carmen.festa@unina.it.
authors: Carmen
authors: C
authors: Festa
authors: CSIR-National Institute of Oceanography, Dona Paula, Goa 403004, India. hadel@nio.org.
authors: Harshada
authors: H
authors: Adel
authors: Department of Pharmacy, University of Naples Federico II (USNF), Naples I-80131, Italy. sidemari@unina.it.
authors: Simona
authors: S
authors: De Marino
authors: EuroEspes Biotechnology, Department of Cellular Immunology, Bergondo 15165, A Coruña, Spain. biotecnologia@ebiotec.com.
authors: Valter
authors: V
authors: Lombardi
authors: CSIR-National Institute of Oceanography, Dona Paula, Goa 403004, India. supriyatilvi@nio.org.
authors: Supriya
authors: S
authors: Tilvi
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, P.O. Box 56, University of Helsinki, Helsinki FI-00014, Finland. dorota.nawrot@helsinki.fi.
authors: Dorota A
authors: DA
authors: Nawrot
authors: Department of Pharmacy, University of Naples Federico II (USNF), Naples I-80131, Italy. azampell@unina.it.
authors: Angela
authors: A
authors: Zampella
authors: CSIR-National Institute of Oceanography, Dona Paula, Goa 403004, India. lisette@nio.org.
authors: Lisette
authors: L
authors: D'Souza
authors: Department of Pharmacy, University of Naples Federico II (USNF), Naples I-80131, Italy. madauria@unina.it.
authors: Maria Valeria
authors: MV
authors: D'Auria
authors: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, P.O. Box 56, University of Helsinki, Helsinki FI-00014, Finland. paivi.tammela@helsinki.fi.
authors: Päivi
authors: P
authors: Tammela
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification*; D000998:Antiviral Agents / Q000302:isolation & purification*; D002646:Chikungunya virus / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D004224:Diterpenes