Discovery of tetrahydrothiazolopyridine-incorporated curcumol derivatives as novel and highly potent anti-cancer agents.

Herein, the structural modification of curcumol via a privileged scaffold incorporation strategy has been demonstrated, which enables the production of a class of novel tetrahydrothiazolopyridine-containing derivatives. Among them, the analogs with an ortho- or meta-substituted benzoyl exhibited superior in vitro anti-proliferative activity, and 9b with a 2, 3-dimethylbenzoyl group showed the most potent activity and good selectivity. Furthermore, 9b showed good in vivo anti-cancer activity and could efficiently suppress the migration of cancer cells, while no apparent toxicity was observed. Further mechanistic studies revealed that 9b exhibited an ability to induce G2/M-phase arrest in cancer cells associated with the disruption of tubulin polymerization. In particular, 9b could efficiently repress self-renewal of cancer stem cells. Overall, our findings highlight 9b as a promising lead compound in cancer therapy.