Saccharothrixones A–D, Tetracenomycin-Type Polyketides from the Marine-Derived Actinomycete Saccharothrix sp. 10-10

Abstract

Saccharothrixones A-C (1-3), three new aromatic polyketide seco-tetracenomycins, and saccharothrixone D (4), a new tetracenomycin analogue possessing opposite configurations at all of the stereogenic centers, were isolated from the marine-derived actinomycete Saccharothrix sp. 10-10. Compounds 1-3 represent the first examples of seco-tetracenomycins where the quinone ring B is cleaved and re-formed into a furanone ring. Their structures were elucidated by spectroscopic analyses and ECD calculations. The absolute configuration of 4 was confirmed by single-crystal X-ray diffraction analysis. Saccharothrixone D (4) showed in vitro cytotoxic activity against the HepG2 cancer cell line with an IC50 value of 7.5 μM.

Marine natural products

“…Saccharothrixone D is unusual in that it has the opposite chirality to Tcm C at each stereocentre. 39 Another innovative genome-mining approach is patternbased and employs molecular networking. This approach was applied to 35 Salinospora samples across the three dened species.…”

N‐Acetylgalactosamine‐Targeted Delivery of Dendrimer‐Doxorubicin Conjugates Influences Doxorubicin Cytotoxicity and Metabolic Profile in Hepatic Cancer Cells

“…However, it is important to note that TCM compounds are less potent than the parent DOX, which is indicated by their higher IC 50 values . For example, Gan et al reported an IC 50 of 7.5 × 10 –6 m for TCM X in HepG2 cells compared to an IC 50 of 1.6 × 10 –6 m for DOX . The TCM F1 methylester analogue ([M–H] – : 379.0823) appeared in the intracellular extracts of P1‐ and P2‐treated cells at similar quantities (Figure , Panel B), which indicates that this metabolite is generated from the P1/P2 conjugates by intracellular enzymes.…”

“…(Figure , Panel B). These molecules are similar in exact mass to tetracenomycin (TCM) compounds, which are structural isomers of DOX metabolites that are known to exhibit similar cytotoxicity via DNA intercalation, topoisomerase II inhibition, and generation of reactive oxygen species (ROS) . Therefore, we chose TCM nomenclature to identify these metabolites.…”

“…Therefore, we chose TCM nomenclature to identify these metabolites. However, it is important to note that TCM compounds are less potent than the parent DOX, which is indicated by their higher IC 50 values . For example, Gan et al reported an IC 50 of 7.5 × 10 –6 m for TCM X in HepG2 cells compared to an IC 50 of 1.6 × 10 –6 m for DOX .…”

Precursor-directed in situ synthesis of Saccharothriolides G and H by the Actinomycete Saccharothrix sp. A1506

“…1,2 Genus Saccharothrix is a rare actinomycete that has furnished an increasing number of bioactive metabolites. [3][4][5][6][7] Our recent studies of Saccharothrix sp. A1506 have afforded saccharothriolides A-F (3-8) (Supplementary Figure S1).…”