Studies Of The Anti-glioma Constituents Of Three Marine Bacteria

Gliomas are one of the most malignant brain tumors. The current chemotherapy and treated strategy are not satisfactory. There is therefore a need to develop novel anti-glioma agents for treating malignant gliomas. Natural products especially marine natural products are highly significant sources of drug leads. In this thesis, the chemical constituents from marine bacteria Streptomyces sp. strain 182SMLY and two unidentified strains ZQ4-23 and P81-A were investigated. The activity of the isolated compounds from the three bacteria against the proliferation of different glioma cells was also evaluated. A total of 11 constituents including five new compounds were obtained in this study. Based on the analyses of the NMR and HRESIMS data as well as the ECD calculation, these new compounds were determined as N-acetyl-N-demethylmayamyc in.. streptoanthraquinone A、(-)-streptophenazine M、 (-)-streptophenazine N, and (-)-streptophenazine O. Streptoanthraquinone A possessed a unique structure, which is signifcantly different from the members of its family. Both N-acetyl-N-demethylmayamycin and streptoanthraquinone A remarkably suppressed the proliferation of four different glioma cells and induced apoptosis in glioma cells. N-acetyl-N-demethylmayamycin also significantly reduced the expression level of PFKFB3, an important metabolic regulator in glioma cells, suggesting that the anti-glioma activity of N-acetyl-N-demethylmayamycin might relate to the tumor metabolism.