Structure–activity relationship of neuritogenic spongean acetylene alcohols, lembehynes

Two new long-chain acetylene alcohols named lembehynes B ( 2 ) and C ( 3 ) were isolated from an Indonesian marine sponge of Haliclona sp. Lembehynes B ( 2 ) and C ( 3 ), which have different types of long carbon-chain parts compared with that of lembehyne A ( 1 ), also exhibited neuritogenic activity against a neuroblastoma cell line, Neuro 2A. For structure–activity relationship study of lembehynes, analogue-I ( 4 ), analogue-II ( 5 ) and analogue-III ( 6 ), which have different types of long carbon-chain parts, were synthesized from suitable fatty acids. As a result of neurite outgrowth assay for these related compounds, it was revealed that the carbon-chain length is important for neuritogenic activity, while the unsaturated bonds in the long-chain part are not. On the other hand, analogue-IV ( 7 ) with 3 S configuration showed much weaker activity than analogue-III ( 6 ) with 3 R configuration and the same type of long carbon-chain part. This indicates the importance of the stereochemistry of the hydroxyl group at C-3 in lembehynes for neuritogenic activity.