Glucopiericidin C: a cytotoxic piericidin glucoside antibiotic produced by a marine Streptomyces isolate

The Journal of Antibiotics
2011.0

Abstract

More than 35 naturally occurring piericidins and closely related antibiotics have been reported, exhibiting diverse biological activities. In our search for new secondary metabolites from marine bacteria, we isolated a new cytotoxic piericidin derivative, glucopiericidin C (3), and for the first time as a natural product, 5-oxo-5-o-tolyl-pentanoic acid (8a), together with 10 known metabolites. The algal metabolite spatozoate (6) was also first isolated from bacteria. The crude extract of the marine-derived Streptomyces isolate B8112 showed moderate activity against Gram-positive/negative bacteria and Candida albicans, strong activity against Mucor miehei, and potent in vitro antitumor activity (mean IC70 < 10 μg ml⁻¹) in a six-cell line panel. Glucopiericidin C was structurally characterized using NMR and MS: it has the molecular formula C₃₀H₄₅NO₈, featuring a 5'-demethoxypiericidin A aglycone with a hexose moiety linked at the C-10 position. It exhibited antibacterial activity comparable to glucopiericidin A against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, activity against Chlorella vulgaris, and concentration-dependent cytotoxicity against 36 human tumor cell lines (mean IC50 2.0 μM, mean IC70 4.2 μM). A Compare Analysis with 100 reference compounds suggested a novel mode of action. Spatozoate was confirmed as a bacterial metabolite, and 5-oxo-5-o-tolyl-pentanoic acid as a natural product for the first time.

Knowledge Graph

Similar Paper