Antimitotic activity of a dithiolpyrrolone from Streptomyces sp. recovered from the Brazilian tunicate Eudistoma vannamei

Eudistoma vannamei is an endemic tunicate from the northeastern Brazilian coast and, yet, the most abundant species in the state of Ceará. Previous studies have shown the hydromethanolic extract to be highly active against cultured tumor cells. Bioassay-guided fractionation yielded novel highly cytotoxic staurosporines. Natural staurosporines have frequently been obtained from actinomycetes, and so, the microbiota associated to this tunicate was investigated for their biomedical potential. Bacterial strains isolate from crushed specimens of the tunicate were elected based on phenotypical characteristics, up-scale grown and extracted with ethyl acetate. Extracts obtained from microorganisms were screened for cytotoxicity in tumor cell lines and one, identified as Streptomyces sp., presented the highest cytotoxicity. This extract was then grown in large quantities, and fractionated using a cytotoxicity-guided approach to yield the dithiolopyrrolone N-(4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl)-N-methyl-formamide. The compound presented IC₅₀ ranging from 1.68 to 3.17µM in various cell lines. Moreover, it induced cell cycle arrest in mitosis, as suggested by flow cytometry and western blot analyses and observation under confocal microscope.