The Antitumor Antibiotics Complex of Aureolic Acids from the Marine Sediment-associated Strain of Streptomyces sp. KMM 9048

Abstract

A new antibiotic complex of six aureolic acids was isolated from the marine sediment-associated strain Streptomyces sp. KMM 9048. Four of the compounds (3–6) were found to be similar but not identical to the known chromomycins A₂, A₃, demethyl chromomycin A₃ and A₄. The two remaining compounds, A_2–1 (1) and A_3–1 (2), were established as novel chromomycin analogs, which did not contain sugar B. Spectroscopic methods including 1D and 2D NMR, and HRMS and MS/MS were applied for structure elucidation. Compounds 1-5 showed strong antimicrobial activity against Gram-positive indicatory bacteria Enterococcus faecium, Staphylococcus aureus, S. epidermidis, and Bacillus subtilis. Antitumor assay indicated that all tested compounds, in different manners, inhibited colony formation of RPMI-7951 and SK-Mel-28 cancer cells. This is the first study reporting the inhibitory effects of chromomycin analogs 1–5 on the colony formation of the investigated cancer cell lines. Compound 3, in a concentration of 5 nM, inhibited colony formation of RPMI-7951 and SK-Mel-28 cells by 82 % and 72 %, respectively. Our finding indicated that, of the compounds tested, 3 and 4 are promising anticancer and antimicrobial agents.