Griseolutein A

Griseolutein acts as a bactericidal agent, its toxicity decreasing with increase in cell density. There is no evidence that griseolutein acts at a specific stage of cell cycle. Inhibition of incorporation of radioactive thymidine into acid-insoluble fraction of cells is marked and rapid, while inhibition of incorporation of uridine also takes place. Incorporation of 32Pi into the acid-insoluble fraction of cells is inhibited while the incorporation into the nucleotide pool is not. Concentration of any of the four deoxyribonucleoside triphosphates in griseolutein-treated cells are similar to or higher than those in untreated cells. No extensive degradation of cellualr DNA is caused by griseolutein. DNA synthesis in plasmolyzed cells in not inhibited by griseolutein.

Fractionation of the extract from the Indonesian Streptomyces sp. ICBB8198 as directed by the antibacterial activity delivered the known phenazine antibiotics griseoluteic acid (1a) and griseolutein A (1b), as well as two new phenazine derivatives (2 and 3). In addition, the known compounds spirodionic acid, dihydrosarkomycins, and 6-ethyl-4-hydroxy-3,5-dimethyl-2H-pyran-2-one (4a), along with the new pyrone 3,6-diethyl-4-hydroxy-5-methyl-2H-pyran-2-one (4b), were isolated. We report here the isolation, structure elucidation, and antibiotic activity of the new metabolites as well as a hypothetical pathway for the formation of the new phenazine derivatives.