LAUSR

Abstract Tubulin polymerisation inhibitors that target colchicine binding site were powerful anticancer agents. Although along the years many colchicine binding site inhibitors (CBSIs) have been reported, few piperidine derivatives were identified as CBSIs. In this regard, we focussed efforts on the piperidine as a promising chemotype to develop potent CBSIs. Herein, novel piperidine derivatives were synthesised and evaluated for their antiproliferative activities. Among them, compound 17a displayed powerful anticancer activity with the IC50 value of 0.81 µM against PC3 cells, which was significantly better than 5-fluorouracil. It could inhibit tubulin polymerisation binding at the colchicine site and inhibit the tumour growth in vitro and in vivo. Further biological studies depicted that 17a suppressed the colony formation, induced apoptosis, and inhibited epithelial-mesenchymal transition against PC3 cells. These results revealed that compound 17a is a promising colchicine binding site inhibitor for the treatment of cancer and it is worthy of further exploitation. Graphical Abstract