Open AccessA novel benzodiazepine derivative that suppresses microtubules dynamics and impairs mitotic progression
Author(s) -
Vittoria Pirani,
Mathieu Métivier,
Emmanuel Gallaud,
Alexandre Thomas,
Siou Ku,
Denis Chrétien,
Roberta Ettari,
Régis Giet,
Lorenzo Corsi,
Christelle Benaud
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.239244
Subject(s) - biology , microtubule , mitosis , microbiology and biotechnology , spindle apparatus , spindle checkpoint , chromosome segregation , tubulin , astral microtubules , colchicine , cell division , cell , chromosome , genetics , gene
A novel 2,3-benzodiazepine-4 derivative, named 1g, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, 1g does not interfere directly with tubulin, nor perturbs microtubules assembly in vitro. The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests it targets a conserved microtubules regulation module in human and flies. Altogether, our results indicate that 1g is a novel promising antimitotic drug with the unique properties altering microtubules growth and mitotic spindle organization.