Synthesis and biological evaluation of novel non-racemic indole-containing allocolchicinoids.

Basic Information

ID: ALA4130488

Journal: Eur J Med Chem

Title: Synthesis and biological evaluation of novel non-racemic indole-containing allocolchicinoids.

Authors: Shchegravina ES, Maleev AA, Ignatov SK, Gracheva IA, Stein A, Schmalz HG, Gavryushin AE, Zubareva AA, Svirshchevskaya EV, Fedorov AY.

Abstract: Two novel indole-containing allocolchicinoids were prepared from naturally occurring colchicine exploiting the Curtius rearrangement and tandem Sonogashira coupling/Pd-catalyzed cyclization as the key transformations. Their cytotoxic properties, apoptosis-inducing activity, tubulin assembly inhibition and short-time cytotoxic effects were investigated. Compound 7 demonstrated the most pronounced anti-cancer activity: IC50 < 1 nM, cell cycle arrest in the G2/M phase, 25% apoptosis induction, as well as lower destructive short-time effects on HT-29 cell line in comparison with colchicine. Docking studies for prepared indole-derived allocolchicine analogues were carried out.

CiteXplore: 29028531

DOI: 10.1016/j.ejmech.2017.09.055

Patent ID: