Indanostatin, a new neuroprotective compound from Streptomyces sp.

Cerebral ischemia is a leading cause of death and long-term disabilities worldwide. In brain ischemia, blood flow disruptions limit the supply of oxygen and glucose to neurons, initiating excitotoxic events. These include activation of glutamate receptors and release of excess glutamate. They induce neuron depolarization and significant increase of intracellular calcium, which activates multiple intracellular death pathways.¹ Accumulation of extracellular glutamate also inhibits cystine-glutamate exchanger, resulting in depletion of the intracellular antioxidant glutathione.^{2, 3} In such conditions, reactive oxygen species are generated and implicated in neuronal cell death.⁴

C6 glioma cells were originally derived from rat neural tumors induced by N-nitrosomethylurea.⁵ The cells still maintain the characteristics of glial cells and undergo cell death when exposed to glutamate. Thus, they provide a good model for evaluating neuroprotective activity against glutamate toxicity. Several chemicals including antioxidants have been reported to inhibit glutamate-induced cytotoxicity in C6 cells.^{6, 7, 8} In this study, microbial metabolites were screened to find neuroprotective compounds against glutamate toxicity. As a result, a new active compound designated indanostatin (1) was isolated from the cultured broth of Streptomyces sp. RAI20.

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