A high-content screen for anti-mitosis and polyploidy-induction identifies an unknown activity of two benzophenanthridine alkaloids from Corydalis longicalcarata. (February 2021)

• Record Type: Journal Article
• Authors: Li, Jinhua; Yan, Ziqi; Li, Hongmei; Shi, Qiong; Huang, Linfang; Nimishetti, Naganna; Allen, Thaddeus D.; Yang, Dun; Zhang, Jing
• Is Part Of: Phytochemistry letters. Volume 41(2021)
• Page Start: 180
• Page End: 185
• Publication Date: 2021-02
• Subjects: DAPI 4′, 6′-diamidino-2-phenylindole -- DMSO Dimethyl Sulfoxide -- EA ethyl acetate -- EtOH ethanol -- HPLC high pressure liquid chromatography -- LC-M liquid chromatography mass spectrometry -- MeOH methanol -- MPLC medium pressure liquid chromatography -- NMR nuclear magnetic resonance -- PE petroleum ether -- TLC thin layer chromatography; High-Throughput screen -- Mitosis -- Polyploidy -- Acetylcorynoline -- Corynoline; Botanical chemistry -- Periodicals; Chimie végétale -- Périodiques; 572.205
• DOI: 10.1016/j.phytol.2020.12.001
• Languages: English
• ISSNs: 1874-3900

Abstract

Graphical abstract: Highlights: A high-content screen was performed using 17, 000 extracts from >2, 000 medicinal plants. An extract from C. longicalcarata was identified as having anti-mitotic and polyploidy-inducing activity. Bioassay-guided isolation was used to identify active components, corynoline and acetylcorynoline. The findings ascribe novel anti-mitotic and polyploidy-inducing activity to these phytochemicals. Abstract: 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.