RESUMO
A neuroprotective compound (2) was isolated from the culture broth of the dutomycin (1) producer Streptomyces sp. RAP78. The molecular formula of 2 was established as C44H55NO16 by high-resolution FAB-MS. The structure was determined to be a new dutomycin derivative possessing an acetimidoyl group in place of an acetyl group by NMR spectroscopic analysis. 13-Deoxo-13-iminodutomycin (2) but not dutomycin (1) protected C6 rat glioma cells and N18-RE-105 rat primary retina-mouse neuroblastoma hybrid cells from glutamate-induced toxicity with EC50s of 0.12 µM and 0.72 µM, respectively.
Assuntos
Fármacos Neuroprotetores/farmacologia , Streptomyces/química , Animais , Antraciclinas , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Descoberta de Drogas , Ácido Glutâmico/toxicidade , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/isolamento & purificação , Ratos , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
A neuroprotective compound designated pyroxazone (1) was isolated from the culture broth of Streptomyces sp. RAN54. The molecular formula of 1 was established as C18H14N2O5 by high-resolution FAB-MS. The structure was determined to be a new 2-amino-3H-phenoxazin-3-one derivative by NMR spectroscopic analysis. Pyroxazone (1) protected C6 rat glioma cells and N18-RE-105 rat primary retina-mouse neuroblastoma hybrid cells from glutamate-induced toxicity with EC50s of 8.2 µM and 1.7 µM, respectively.