A high-content screen for anti-mitosis and polyploidy-induction identifies an unknown activity of two benzophenanthridine alkaloids from Corydalis longicalcarata

Natural sources are a valuable reserve of chemical diversity for drug development. However, creative screening assays are required to unlock this potential. A high-content screen was developed to isolate anti-mitotic and polyploidy-inducing activity in mammalian cancer cells from plant extracts. The assay was utilized in an analysis of more than 2000 medicinal plants and activity was identified in a rhizome extract from Corydalis longicalcarata . Two bioactive benzophenanthridine alkaloids, corynoline and its close analog acetylcorynoline, were purified. These compounds display pleiotropic effects on cell division, including prevention of chromosome congression, compromise of the spindle checkpoint response, and blockade of cytokinesis. Corynoline and acetylcorynoline are known entities but the potential for development as anti-mitotic drugs has never been ascribed to these two phytochemicals. This study highlights the requirement and ability of novel bioassays to unlock novel function for known phytochemicals.