Synthesis of marmycin A and investigation into its cellular activity

Anthracyclines such as doxorubicin are used extensively in the treatment of cancers. Anthraquinone-related angucyclines also exhibit antiproliferative properties and have been proposed to operate via similar mechanisms, including direct genome targeting. Here, we report the chemical synthesis of marmycin A and the study of its cellular activity. The aromatic core was constructed by means of a one-pot multistep reaction comprising a regioselective Diels-Alder cycloaddition, and the complex sugar backbone was introduced through a copper-catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does not target the nucleus but instead accumulates in lysosomes, thereby promoting cell death independently of genome targeting. Furthermore, a synthetic dimer of marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic activity against the invasive MDA-MB-231 cancer cell line. These findings shed light on the elusive pathways through which anthraquinone derivatives act in cells, pointing towards unanticipated biological and therapeutic applications

Manure contaminated with the antibiotic sulfadiazine impairs the abundance of nirK- and nirS-type denitrifiers in the gut of the earthworm Eisenia fetida.

The antibiotic sulfadiazine (SDZ) can affect denitrifying bacteria in soil. However, effects on denitrifiers in the gut of earthworms have not been described so far. Therefore, the influence of SDZcontaminated manure applied to soil on denitrifiers in the gut of the earthworm Eisenia fetida was assessed by quantitative PCR targeting genes coding for nirK- and nirS- type nitrite reductases of denitrifiers. Gut contents of Eisenia fetida contained 2.5 x 106 and 5.1 x 105 gene copies of nirK and nirS, respectively, after two weeks in soils amended with manure only. Copy numbers of nirK and nirS in gut contents from manure treatments with SDZ were up to 10 times less. Overall, the data indicate a negative impact of SDZ on denitrifiers in the gut of earthworms