Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo

The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.

Automated summary

The increasing resistance to antibiotics poses a significant threat to human health. This study identifies the strong antibiotic activity of myxocoumarin B, a natural product from Stigmatella aurantiaca MYX-030, against various clinically relevant bacterial pathogens. The study also synthesizes structural analogs to explore structure-activity relationships and potential synthetic access. This research highlights the exceptional antibiotic activity of the myxocoumarin scaffold, suggesting its potential for developing novel antibiotics.