A New Simplified Coralmycin Derivative with Potent Anti-Gram-Negative Activity and Its Congeners Produced by the Myxobacterium Corallococcus coralloides M23.

Multidrug-resistant (MDR) Gram-negative bacterial infections urgently require new antibacterial agents with novel chemical scaffolds. In our continued investigation of minor metabolites produced by the myxobacterium Corallococcus coralloides M23, we isolated three new coralmycin derivatives, coralmycins J (1), K (2), and L (3), from large-scale fermentation cultures. Spectroscopic analyses revealed that these compounds represent structurally simplified derivatives of coralmycin with varying degrees of truncation. Compounds 1-4 (coralmycins J, K, L, and A) are new natural products isolated in our recent and current studies, while compound 5 (cystobactamid 919-2) is the externally reported reference compound used for comparison. Compound 1 exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria and effectively inhibited E. coli DNA gyrase, whereas compounds 2 and 3 showed no detectable biological activity. Structure-activity relationship studies suggested that the β-methoxyasparagine moiety, ring C, or both, are important for antibacterial activity and DNA gyrase inhibition, whereas rings A and B present in compounds 4 and 5 appear to be dispensable. These findings provide valuable insights into the structural simplification of hexapeptidic coralmycins for the development of therapeutic agents against multidrug-resistant Gram-negative bacterial infections.