New Hygrocins K–U and Streptophenylpropanamide A and Bioactive Compounds from the Marine-Associated <i>Streptomyces</i> sp. ZZ1956

Abstract

Marine-derived Streptomyces actinomycetes are one of the most important sources for the discovery of novel bioactive natural products. This study characterized the isolation, structural elucidation and biological activity evaluation of thirty compounds, including twelve previously undescribed compounds, namely hygrocins K–U (5–13, 17 and 18) and streptophenylpropanamide A (23), from the marine-associated actinomycete Streptomyces sp. ZZ1956. Structures of the isolated compounds were determined by a combination of extensive NMR spectroscopic analyses, HRESIMS data, the Mosher’s method, ECD calculations, single crystal X-ray diffraction and comparison with reported data. Hygrocins C (1), D (2), F (4), N (8), Q (11) and R (12), 2-acetamide-6-hydroxy-7-methyl-1,4-naphthoquinone (22), echoside C (27), echoside A (28) and 11,11′-O-dimethylelaiophylin (30) had antiproliferative activity (IC50: 0.16–19.39 μM) against both human glioma U87MG and U251 cells with hygrocin C as the strongest active compound (IC50: 0.16 and 0.35 μM, respectively). The analysis of the structure–activity relationship indicated that a small change in the structures of the naphthalenic ansamycins had significant influence on their antiglioma activities. Hygrocins N (8), O (9), R (12), T (17) and U (18), 2-amino-6-hydroxy-7-methyl-1,4-naphthoquinone (21), 2-acetamide-6-hydroxy-7-methyl-1,4-naphthoquinone (22), 3′-methoxy(1,1′,4′,1″-terphenyl)-2′,6′-diol (26), echoside C (27) and echoside A (28) showed antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli with MIC values of 3–48 μg/mL.

Keywords

• marine <i>Streptomyces</i> sp. ZZ1956
• Streptomycetaceae
• hygrocins K–U
• streptophenylpropanamide A
• structure elucidation
• antiglioma activity