Coralmycin Derivatives with Potent Anti-Gram Negative Activity Produced by the Myxobacteria Corallococcus coralloides M23

Seven new coralmycin derivatives, coralmycins C ( ), D ( ), E ( ), F ( ), G ( ), H ( ), and I ( ), along with three known compounds, cystobactamids 891-2 (8), 905-2 (9), and 507 (10), were isolated from a large-scale culture of the myxobacteria M23. The structures of these compounds, including their relative stereochemistries, were elucidated by interpretation of their spectroscopic and CD data. The structure-activity relationships of their antibacterial and DNA gyrase inhibitory activities indicated that the -nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the -nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including and , and the β-methoxyasparagine moiety could affect cellular uptake into all tested bacteria. These results could facilitate the chemical optimization of coralmycins for the treatment of multidrug-resistant Gram-negative bacteria.