High content live cell imaging for the discovery of new antimalarial marine natural products

摘要: Background: The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths year, number that could rise due increasing multi-drug resistance all antimalarial drugs currently available. Therefore, there an urgent need the discovery of new drug therapies. Recently, our laboratory developed simple one-step fluorescence-based live cell-imaging assay integrate complex biology into discovery. Here we used newly platform discover novel marine natural products and their cellular phenotypic effects against most lethal parasite, Plasmodium falciparum. Methods: A high content cell imaging was screen extracts on malaria. Parasites were grown vitro presence extracts, stained with RNA sensitive dye, imaged at timed intervals BD Pathway HT automated confocal microscope. Results: Image analysis validated methodology larger scale level revealed potential activity selected minimal cytotoxic effect host red blood cells. To further validate assay, investigated parasite’s phenotypes when incubated purified bioactive product bromophycolide A. We show has strong specific morphological parasites, similar ones observed from initial extracts. Conclusion: Collectively, results high-content (HCLCI) can be chemical libraries identify inhibitors limited effects. All together provide leads antimalarials.