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 similar to 9) was isolated from fermentations of an actinomycete strain X10/78/978 (NCIM B40808), identified as Streptomyces rimosus, during a microbial extract scr eening programme to identify inhibitors of bacterial histidine kinase. The structures of these compounds were elucidated by spectroscopic methods incl uding the HMQC, HMBC and INADEQUATE NMR experiments. The structure of 1 was confirmed by X-ray crystallographic studies. Compounds 5 and 6 were produc ed in fermentations in the presence of NaBr and NaI respectively. The most abundant member of the series, streptopyrrole, 1, inhibited the nitrogen re gulator II (NRII) histidine kinase from Escherichia roll with an IC50 of 20 mu M and exhibited antimicrobial activity against a range of bacteria and fungi.