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.
Shin-Ya
K
K
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan.
Kim
J S
JS
Furihata
K
K
Hayakawa
Y
Y
Seto
H
H
D000818:Animals; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy; D002243:Carbolines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D018698:Glutamic Acid / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control; D013302:Streptomyces / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002243:Carbolines; D018696:Neuroprotective Agents; C427627:mescengricin; D018698:Glutamic Acid