58(P19) 神経成長因子産生促進作用を持つケロウジ由来ジテルペノイド類の構造(ポスター発表の部)

Thelophoraceous brown fungus Sarcodon scabrosus (Fr.) Karst. which grows in coniferous and deciduous woods of Europe and Japan has been recognized as an inedible mushroom because of its strongly bitter taste which may derive from bitter terpenoids. During our studies on biologically active constituents of Japanese mushrooms (Basidiomycetes), we found a new diterpenoids which showed strong inductive activity of the nerve growth factor (NGF) synthesis in 1321N1 human astrocytoma cells, from S. scabrosus. The fruit body (1.4 kg) of S. scabrosus was extracted with MeOH and then the extract was partitioned between n-hexane-EtOAc and water. The n-hexane-EtOAc extract was subjected repeatedly to silica gel chromatography and reversed-phase HPLC on ODS to give new cyathane diterpenoids, scabronine A (1), G (3) and J (4), and episcabronine A (2). The stereostructures for those compounds (1-4) were elucidated on the bases of the spectroscopic analysis of natural products and their derivatives. Scabronine A (1) and scabronine G methyl ester (7) showed potent inductive activity of the NGF synthesis in 1321N1 human astrocytoma cells. Namely, 1 released 746 pg/mL of NGF at 100 μM from 1321N1 cells under basal release of 147 pg/mL of NGF during two days. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) revealed that 1 increased NGF mRNA by 1.99-fold in 1321 N1 cells. Some NGF inducers such as catecholamines, benzoquinones, hericenones, fellutamides, kansuinin A, pyrroloquinoline quinones and erinacines have been hitherto reported. A strong NGF inducer with low molecular size such as scabronine A (1) or scabronine G methyl ester (7) will be a useful drug for serious neuronal diseases such as Alzheimer's disease. Scabronines will also be helpful to clarify the mechanism of NGF synthesis and secretion.