Identification of pyrroloformamide as a cytokinesis modulator.
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.
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Rua Cel Nunes de Melo 1127, Fortaleza, Ceará, 60430-270 (Brazil).
Paula A
PA
Abreu
Thiciana S
TS
Sousa
Paula C
PC
Jimenez
Diego V
DV
Wilke
Danilo D
DD
Rocha
Hozana P S
HP
Freitas
Otília D L
OD
Pessoa
James J
JJ
La Clair
Letícia V
LV
Costa-Lotufo
D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D048749:Cytokinesis / Q000187:drug effects*; D005559:Formamides / Q000737:chemistry / Q000633:toxicity*; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D018613:Microscopy, Confocal
D005559:Formamides; D006574:Heterocyclic Compounds, 2-Ring; C000592734:N-(4,5-dihydro-5-oxo-1,2-dithiolo(4,3-b)pyrrol-6-yl)-N-methylformamide; C031066:formamide
cell cycle; cytokinesis; mitosis; natural products; pyrrolinonodithioles