Identification of Pyrroloformamide as a Cytokinesis Modulator

• Published in: Chembiochem : a European journal of chemical biology 2014-03, Vol.15 (4), p.501-506
• Main Authors: Abreu, Paula A., Sousa, Thiciana S., Jimenez, Paula C., Wilke, Diego V., Rocha, Danilo D., Freitas, Hozana P. S., Pessoa, Otília D. L., La Clair, James J., Costa-Lotufo, Letícia V.
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; cytokinesis; Cytokinesis - drug effects; Formamides - chemistry; Formamides - toxicity; Heterocyclic Compounds, 2-Ring - chemistry; Heterocyclic Compounds, 2-Ring - toxicity; Humans; Microscopy, Confocal; mitosis; Natural products; pyrrolinonodithioles
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201300717

Discovered in the late 1940s, the pyrrolinonodithioles represent a family of potent disulfide‐containing natural products. Although they are understood in a synthetic and biosynthetic context, the biological role of these materials remains unresolved. To date, their activity has been suggested to arise through regulating RNA metabolism, and more recently they have been suggested to function as backup thiols for detoxification. Using materials identified through a natural products program, we now identify the biological function of one member of this family, pyrroloformamide, as an antimitotic agent acting, in part, by disrupting cytokinesis. Potent and specific mitotic regulation: Discovered in the late 1940s and understood in a synthetic and biosynthetic context, the pyrrolinonodithioles represent a family of potent disulfide natural products whose biological role still remains unresolved. We now identify the biological function of one member of this family, pyrroloformamide, as a modulator of cytokinesis.