S. staurosporeus

S. staurosporeus Anaya Actinomadura madurae A. melliaura Arcyria denudata Aspergillus flavus A. tubingensis Nocardia aerocoligenes Nocardiopsis dassonvillei Nocardiopsis sp. 

In 1990, researchers at Bristol-Myers Squibb reported the isolation of Bmy-41950 (322) from S. staurosporeus strain R10069 (ATCC 55006). This isolate showed in vitro activity against human colon cancer cells (HCT-116) (307). Two years later, Isono et al. reported the isolation of the same natural product from a different Streptomyces sp., S. platensis subsp. malvinus RK-1409 and named it RK-1409 (7-oxostaurosporine) (322) (308,309). In nature, this isolate was obtained in its optically active form [ Id + 38.3 (c 0.06, CHCI3) (309). The PKC inhibitor RK-1409 (7-oxostaurosporine) inhibited the morphological change of a human erythroleukemia cell line, K-562, induced by phorbol 12,13-dibutyrate (PDBu), and also showed a weak antimicrobial activity against Chlorella vulgaris and Pyricularia oryzae (308). 

Isolated in 1977 from the bacterium Streptomyces staurosporeus, staurosporine (3) is a natural product that inhibits most protein kinases at low nanomolar concentrations [23]. Through small-molecule/protein complex cocrystallization, it was shown that staurosporine binds tightly to the adenosine binding pocket ofthe catalytic subunit of the cAMP-dependent protein kinase. Chelerythrine (4) was identified as an inhibitor of Bcl-XL-Bak BH3 peptide binding vdth an IC50 of 1.5 p,M, and also displaced Bax from Bcl-XL [24]. Chelidonine (S) is another example of an alkaloid natural product that inhibits the taxol-mediated polymerization of tubulin in the micromolar range ( 24.0 p,M). 

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