A novel neuronal cell protecting substance mescengricin produced by Streptomyces griseoflavus

Neuronal cell death in brain ischemia reperfusion injury such as stroke was induced by L-glutamate toxicity (Choi, D.W. J. Neurosci. 1990. 10, 2493 2501; Coyle, J.T. and Puttfarcken, P. Science 1993, 262, 689 695). In the course of our screening for neuronal cell protecting substances of microbial origin, we isolated a novel compound designated mescengricin from Streptomyces griseoflavus 2853-SVS4(Kim, J.-S., Shin-ya, K., Furihata, K., Hayakawa, Y. and Seto, H. Tetrahedron Lett. 1997. 38, 3431 3434). The structure of mescengricin was determined by a variety of NMR experiments such as HMBC, D-HMBC (Furihata, K., Seto, H. Tetrahedron Lett. 1995. 36, 2817 2820), 1H 15N HMBC (15N-HMBC). It possesses an alpha-carboline structure substituted by a glycerol-ester and a hydroxydihydropyrone. Mescengricin protected chick primary mesencephalic neurons from L-glutamate toxicity with EC50 value 6.0 nM.