Epolactaene
- Structure
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- Producing organism
- Penicillium sp.
- Biological activity
- induction of neurite outgrowth
- Abstract
- We have screened microbial products to discover neuritogenic compounds which induced neurite outgrowth in the human neuroblastoma cell line SH-SY5Y that lacks significant TRK family mRNAs. During the screening, we isolated a novel, non-protein neurotrophic compound, epolactaene, produced by Penicillium sp. 1689-P, having an epoxide-containing γ-lactam ring in the molecule. However, only small quantities of epolactaene could be isolated from the fungus; furthermore, the compound was unstable under light because of a labile triene group in the side chain and an epoxide fused to a γ-lactam ring. In the present paper, we prepared a number of epolactaene derivatives, 3-substituted 3-pyrrolin-2-ones possessing a double bond in the γ-lactam ring, to find compounds with more effective neuritogenic activity. In addition, we described the structure-activity relationship of 3-substituted 3-pyrrolin-2-ones on the neuritogenic effect in SH-SY5Y cells. MT-5, 3-acetyl-4,5-dimethyl-5-octadecyloxy-3-pyrrolin-2-one, the most effective derivative for neuritogenic activity in SH-SY5Y cells, also arrested cell cycle progression at G0/G1 like epolactaene.
- References
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isolation and structural determination
- Kakeya H, Takahashi I, Okada G, Isono K, Osada H.: Epolactaene, a novel neuritogenic compound in human neuroblastoma cells, produced by a marine fungus.
J Antibiot, 48(7): 733-735 (1995)
biological activity and structure-activity relationship- Nagumo Y, Kakeya H, Shoji M, Hayashi Y, Dohmae N, Osada H.: Epolactaene binds human Hsp60 Cys442 resulting in the inhibition of chaperone activity.
Biochem J, 387(Pt 3): 835-840 (2005) [ doi: 10.1042/BJ20041355 ]- Kakeya H, Onozawa C, Sato M, Arai K, Osada H.: Neuritogenic effect of epolactaene derivatives on human neuroblastoma cells which lack high-affinity nerve growth factor receptors.
J Med Chem, 40(4): 391-394 (1997) [ doi: 10.1021/jm960719a ]- Kakeya H, Osada H.
Induction of neurite outgrowth by epolactaene derivatives, 3-substituted 3-pyrrolin-2-ones.
RIKEN Review 18, 35-36 (1998) [ RIKEN Review: No_18/18_035 ]synthesis by other group- Hayashi Y, Kanayama J, Yamaguchi J, Shoji M.: Diastereoselective total synthesis of both enantiomers of epolactaene.
J Org Chem, 67(26): 9443-9448 (2002) - Kakeya H, Takahashi I, Okada G, Isono K, Osada H.: Epolactaene, a novel neuritogenic compound in human neuroblastoma cells, produced by a marine fungus.