Oligomycins as inhibitors of K-Ras plasma membrane localisation.

ABSTRACT: Frequently present in pancreatic, colorectal and non-small cell lung carcinomas, oncogenic mutant K-Ras must be localised to the plasma membrane (PM) to be functional. Inhibitors of K-Ras PM localisation are therefore putative cancer chemotherapeutics. By screening a microbial extract library in a high content cell-based assay we detected the rare oligomycin class of Streptomyces polyketides as inhibitors of K-Ras PM localisation. Cultivation and fractionation of three unique oligomycin producing Streptomyces strains yielded oligomycins A-E (1-5) and 21-hydroxy-oligomycin A (6), together with the new 21-hydroxy-oligomycin C (7) and 40-hydroxy-oligomycin B (8). Structures for 1-8 were assigned by detailed spectroscopic analysis. Cancer cell viability screening confirmed 1-8 were cytotoxic t

SUBMITTER: Salim AA 

PROVIDER: S-EPMC4689619 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature