A novel benzodiazepine derivative that suppresses microtubules dynamics and impairs mitotic progression

Abstract

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.