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

摘要

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: IC 50 ? Graphical abstract Display Omitted Highlights ? Two pyrrole-based allocolchicinoids were prepared from commercial colchicine. ? Compounds exhibit excellent cytotoxicity towards epithelial cell lines. ? 7 and 12 induced cell accumulation in the G2/M phase in 2D cultures. ? 7 has lower destructive short-time effects on HT-29?cell line in comparison with colchicine.