A New Inhibitor of Microglial Neurotoxicity from Marine-Derived Streptomyces sp.

Abstract

Inflammation in the brain and the rest of the central nervous system (CNS) is a key factor in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Multiple lines of evidence suggest that microglia, the resident immune cells of the CNS, play a critical role in inflammation-mediated neurodegeneration. Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. As part of our continuing interest to discover secondary metabolites from marine microorganisms, we could isolate a new echinosporin derivative from marine Streptomyces sp., possessing strong anti-neuroinflammatory activity as demonstrated by a reduction in nitric oxide (NO) production in LPS-activated BV-2 microglial cells. The structure of the active compound was determined by extensive NMR and mass spectroscopic studies. An unambiguous assignment of the absolute configuration was also achieved by a single-crystal X-ray diffraction (XRD) experiment.immune cells of the CNS, play a critical role in inflammation-mediated neurodegeneration. Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. As part of our continuing interest to discover secondary metabolites from marine microorganisms, we could isolate a new echinosporin derivative from marine Streptomyces sp., possessing strong anti-neuroinflammatory activity as demonstrated by a reduction in nitric oxide (NO) production in LPS-activated BV-2 microglial cells. The structure of the active compound was determined by extensive NMR and mass spectroscopic studies. An unambiguous assignment of the absolute configuration was also achieved by a single-crystal X-ray diffraction (XRD) experiment.