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 3S configuration showed much weaker activity than analogue-III (6) with 3R 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. (C) 2002 Elsevier Science Ltd. All rights reserved.