Novel streptopyrroles from Streptomyces rimosus with bacterial protein histidine kinase inhibitory and antimicrobial activities.

A series of halogenated pyrrolo [2,1-b] [1,3] benzoxazines (1 approximately 9) was isolated from fermentations of an actinomycete strain X10/78/978 (NCIMB40808), identified as Streptomyces rimosus, during a microbial extract screening programme to identify inhibitors of bacterial histidine kinase. The structures of these compounds were elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments. The structure of 1 was confirmed by X-ray crystallographic studies. Compounds 5 and 6 were produced in fermentations in the presence of NaBr and NaI respectively. The most abundant member of the series, streptopyrrole, 1, inhibited the nitrogen regulator II (NRII) histidine kinase from Escherichia coli with an IC50 of 20 microM and exhibited antimicrobial activity against a range of bacteria and fungi.