New aminocoumarin compounds, designated novclobiocins, useful as broad-spectrum antibiotics and cytotoxic agents, prepared sing genetically modified bacterial strains

摘要

New aminocoumarin compounds (I), designated novclobiocins, consist of clorobiocin analogs containing modified N-acyl residues and/or 8-substituents. Aminocoumarin compounds of formula (I) are new. R1mono-, di- or trisubstituted benzoyl, mono- or disubstituted phenylpropionyl, phenylacetyl or mono- or disubstituted cinnamyl; R2OH, alkyl or halo; R3, R4OH or 5-(R5)-pyrrol-2-ylcarbonyl; R5Me, halo or halomethyl. Independent claims are included for two biotechnological methods for preparing (I). [Image] ACTIVITY : Antibiotic; Cytostatic. Novclobiocin 225 (Ia) had minimum inhibitory cconcentration values (in mu g/ml) of 16 against Staphylococcus aureus 80CR5, 0.06 or less against Staphylococcus aureus ATCC 29213 and ATCC 43300, 1 against Streptococcus pneumoniae ATCC 49619, 8 against Escherichia coli DC2 and 0.5 against Pseudomonas aeruginosa K799/61. MECHANISM OF ACTION : Bacterial gyrase inhibitor. (Ia) had IC50 45 nM for inhibition of bacterial gyrase.