Dechlororoseophilin: a new cytotoxic metabolite from Streptomyces griseoviridis

The producing organism was cultivated in 500-ml Erlenmeyer flasks containing 100 ml of a medium consisting of glycerol 4.0%, soybean meal 1.5%, molasses 1% and calcium carbonate 0.4% (pH 6.8) on a rotary shaker at 27 °C for 5 days. The fermentation broth (2.0 l) was centrifuged and the mycelium was extracted with acetone. After evaporation, the aqueous concentrate was extracted with ethyl acetate. The extract was applied to a silica gel column, which was washed with chloroform–methanol (10:1) and eluted with chloroform–methanol–29% ammonia water (200:20:1). The eluted pigment was subjected to reversed-phase HPLC (XBridge C₁₈, Waters Corporation, Milford, MA, USA) using 88% methanol with 0.2% triethylamine. A pigment fraction was concentrated and dissolved in ethyl acetate. After the solution was washed with 0.1 M hydrochloric acid and water, the organic layer was concentrated to dryness to give a red powder of 1 (8.2 mg). The physico-chemical properties of 1 are summarized as follows: m.p. 81–86 °C; high-resolution FAB-MS m/z 419.2697 (MH⁺, calcd for C₂₇H₃₅N₂O₂, 419.2701); UV λ_max (ɛ) 536 nm (142 000) in methanol, 536 nm (143 000) in 0.01 M HCl—methanol, 300 nm (43 400), 485 nm (42 100) in 0.01 M NaOH—methanol; IR (KBr) ν_max 3450, 2910, 1590, 1290 cm⁻¹.

The cytotoxic activities of 1 and roseophilin were examined by using four tumor cell lines. The cells were plated and incubated for 3 days with various concentrations of samples. After the cells were treated with 0.5 mg ml⁻¹ of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) for 4 h at 37 °C, cell growth was measured as absorbance at 570 nm. The IC₅₀ values for dechlororoseophilin and roseophilin were 2.6 and 1.0 μM against HT-1080 human fibrosarcoma cells, 2.1 and 0.72 μM against C6 rat glioma cells, 2.7 and 2.1 μM against MCF7 human breast cancer cells, and 2.0 and 1.9 μM against T-47D human breast cancer cells, respectively.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD