Coralmycin derivatives with potent anti-gram negative activity produced by the myxobacteria Corallococcus coralloides M23

Abstract

Seven new coralmycin derivatives, coralmycins C (1), D (2), E (3), F (4), G (5), H (6), and I (7), 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 Corallococcus coralloides 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 para-nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the para-nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae, and the -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.