Cytotoxic and Antibacterial Marfuraquinocins from the Deep South China Sea-Derived <named-content content-type="genus-species" type="simple">Streptomyces niveus</named-content> SCSIO 3406

Four new sesquiterpenoid naphthoquinones, marfuraquinocins A−D (1−4), and two new geranylated phenazines, phenaziterpenes A (5) and B (6), were isolated from the fermentation broth of Streptomyces niveus SCSIO 3406, which originated from a South China Sea sediment sample obtained from a depth of 3536 m. The structures of 1−6 were elucidated on the basis of extensive MS and one-dimensional and two-dimensional NMR spectroscopic analyses. In a panel of cytotoxicity and antibacterial assays, 1 and 3 were found to inhibit a NCI-H460 cancer cell line with IC50 values of 3.7 and 4.4 μM, respectively. Compounds 1, 3, and 4 exhibited antibacterial activities against Staphylococcus aureus ATCC 29213 with equivalent MIC values of 8.0 μg/mL; compounds 3 and 4 each showed antibacterial activity against methicillin-resistant Staphylococcus epidermidis (MRSE) shhs-E1 with MIC values of 8.0 μg/mL. A play an important role in supplying bioactive natural products with clinical or pharmaceutical applications. In the last several decades, a greater focus has been placed on studying actinomycetes from marine environments, and they have proven to be a productive new source for novel anticancer and antibacterial agents. In our efforts to explore anti-infective and cytotoxic metabolites from marine-derived actinomycetes originating from the South China Sea, we have reported antimalarial alkaloids and a cytotoxic cyclopeptide from Marinactinospora thermotolerans SCSIO 00652, cytotoxic angucyclines from Streptomyces lusitanus SCSIO LR32, and an unusual pregnene-based steroid from Streptomyces sp. SCSIO 03219. Recently, we found that the fermentation extract of another deep South China Sea sediment-derived actinomycete, identified as Streptomyces niveus SCSIO 3406, showed antibacterial activity against methicillin-resistant Staphylococcus epidermidis (MRSE) shhs-E1 and cytotoxic activity against a panel of human tumor cell lines. Subsequent chemical investigation of the fermentation broth of this strain led to the isolation of six new compounds, including four sesquiterpenoid naphthoquinones, named marfuraquinocins A−D (1−4), and two geranylated phenazines, named phenaziterpenes A (5) and B (6). In this paper, we report the fermentation, isolation, structure elucidation, as well as cytotoxic and antibacterial activities of these compounds. ■ RESULTS AND DISCUSSION Strain S. niveus SCSIO 3406 was fermented on a 24 L scale in individual 1 L Erlenmeyer flasks. The fermentation extract was subjected to silica gel column chromatography and semipreparative HPLC, affording compounds 1−6. Marfuraquinocin A (1) was isolated as a yellow solid. Its molecular formula (C26H32O5) was determined upon analysis of the HRESIMS peak at m/z 425.2313 [M + H]; this molecular formula afforded 11 degrees of unsaturation. The UV spectrum of 1 showed absorption peaks at 415, 301, 264 and 221 nm, indicating the presence of a highly conjugated system. Its IR Received: July 25, 2013 Published: November 19, 2013 Article