title: Spongiapyridine and related spongians isolated from an Indonesian Spongia sp.
abstract: New compounds 18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one (1), 18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one (2), and spongiapyridine (3) and the known compound 17-hydroxy-4-epi-spongialactone A (4) were isolated from an Indonesian sponge of the genus Spongia. The structures of 1-3 were deduced by analyses of physical and spectroscopic data. Diterpene 3 is unusual, as the D-ring is a pyridyl ring system rather than the standard δ-lactone. The structure elucidation of this compound was complicated by facile exchange of the axial proton at the C-11 methylene with deuterium from methanol-d4. The isolated compounds were tested for biological activity in a battery of in vitro assays (TNF-α-induced NFκB, LPS-induced iNOS, RXR stimulation, quinone reductase 1 induction, aromatase inhibition, TRPM7 ion channels, and aspartic protease BACE1 inhibition). Norditerpene 2 modestly inhibited aromatase with an IC50 of 34 μM and induced quinone reductase 1 activity with a CD (the concentration needed to double the enzymatic response) of 11.2 μM. The remaining isolates were inactive.
authors.affiliation: Department of Chemistry, University of Hawaii at Manoa , Honolulu, Hawaii 96822, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Parrish
authors.forename: Wesley Y
authors.initials: WY
authors.lastname: Yoshida
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Michelle
authors.initials: M
authors.lastname: Kelly
authors.forename: Philip G
authors.initials: PG
authors.lastname: Williams
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011161:Porifera / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C000591524:18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one; C000591525:18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one; D004224:Diterpenes; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C000591526:spongiapyridine; D016660:NAD(P)H Dehydrogenase (Quinone)