title: Seed dormancy breaking diterpenoids from the liverwort Plagiochila sciophila and their differentiation inducing activity in human promyelocytic leukemia HL-60 cells.
abstract: To obtain the structural diversity of bioactive compounds similar to cotylenins and fusicoccins that modulate 14-3-3 protein-protein interactions in eukaryotes, screening tests were carried out using the lettuce seed dormancy breaking-assay. An acetone extract of the liverwort Plagiochila sciophila exhibited significant activity against the seeds in the presence of the plant hormone abscisic acid. Activity-guided fractionation of the extract afforded the isolation of seven novel fusicoccane-type diterpenoids, named fusicosciophins A-E (1-5), 8-deacetyl (6) and 9-deacetyl fusicosciophin E (7). Their structures were determined by spectroscopic methods and X-ray crystallographic analyses. All the pure isolated compounds (1-7) exhibited moderate lettuce seed dormancy breaking activity. In addition, the differentiation-inducing activity and cytotoxicity of these isolates, together with fusicoccin A (FC-A) and all-trans retinoic acid (ATRA), were evaluated in human promyelocytic leukemia HL-60 cells and human mouth epidermal carcinoma KB cells, respectively. Fusicosciophins (2 and 4) and FC-A exhibited moderate differentiation-inducing activity (EC50 31.2-59.1 microM) compared with ATRA (EC50 0.3 microM), while 2, 4 and ATRA exhibited higher selectivity indices (IC50/EC50 >3.38-667) than FC-A (IC50/EC50 1.05). This is the first report on the isolation of fusicoccane-type diterpenoids from liverworts having seed dormancy breaking activity and differentiation-inducing activity in mammal cells.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kenmoku
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tada
authors.forename: Megumi
authors.initials: M
authors.lastname: Oogushi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Esumi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Noji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sassa
authors.forename: Masao
authors.initials: M
authors.lastname: Toyota
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asakawa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D018525:Germination / Q000187:drug effects*; D018922:HL-60 Cells; D035926:Hepatophyta / Q000502:physiology*; D006801:Humans; D007624:KB Cells; D018545:Lactuca / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D012639:Seeds / Q000502:physiology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D011083:Polycyclic Compounds