Isolation and structure determination of two novel phenazines from a Streptomyces with inhibitory activity against metallo-enzymes, including metallo-beta-lactamase.
Two novel metabolites, SB 212021 and SB 212305, have been isolated from a Streptomyces and shown to have molecular formulae of C15H10N2O5 and C20H17N3O8S, respectively. The structures were deduced by a combination of NMR techniques and mass spectral fragmentation patterns and shown to be novel members of the phenazine group of antibiotics. In the absence of added zinc, both compounds had IC50's of 1-75 microM for the Bacteroides fragilis 262 CfiA and Xanthomonas maltophilia L-1 metallo-beta-lactamases. The compounds also inhibited ACE with IC50's of 55 and 68 microM, respectively. Mode of action studies illustrate that the compounds inhibit some metalloenzymes by chelation of the active site metal ion. They exhibit poor antibacterial activity.
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005285:Fermentation; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010619:Phenazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013302:Streptomyces; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D010619:Phenazines; C096928:SB 212021; C096929:SB 212305; D008666:Metalloendopeptidases