Seco-tetracenomycins from the marine-derived actinomycete saccharothrix sp. 10-10

Abstract

Six new tetracenomycin congeners, saccharothrixones E–I (1–5) and 13-de-O-methyltetracenomycin X (6), were isolated from the rare marine-derived actinomycete Saccharothrix sp. 10-10. Their structures were elucidated by spectroscopic analysis and time-dependent density functional theory (TDDFT)-electronic circular dichroism (ECD) calculations. Saccharothrixones G (3) and H (4) are the first examples of tetracenomycins featuring a novel ring-A-cleaved chromophore. Saccharothrixone I (5) was determined to be a seco-tetracenomycin derivative with ring-B cleavage. The new structural characteristics, highlighted by different oxidations at C-5 and cleavages in rings A and B, enrich the structural diversity of tetracenomycins and provide evidence for tetracenomycin biosynthesis. Analysis of the structure–activity relationship of these compounds confirmed the importance of the planarity of the naphthacenequinone chromophore and the methylation of the polar carboxy groups for tetracenomycin cytotoxicity.