Design, synthesis and bioactivity evaluation of coumarin-chalcone hybrids as potential anticancer agents

The selenoprotein thioredoxin reductases (TrxRs) have been extensively studied as a potential target for the development of anticancer drugs. Herein, we designed, synthesized, and evaluated a series of coumarin-chalcone hybrids as TrxR inhibitors. Most of them exhibited enhancing anticancer activity than Xanthohumol (Xn). The representative Xn-2 (IC₅₀ = 3.6 μM) was a fluorescence agent, wherein drug uptake can be readily monitored in living cells by red fluorescence imaging. Xn-2 down-regulated the expression of TrxR, remarkedly induced ROS accumulation to activate mitochondrial apoptosis pathway. Furthermore, Xn-2 inhibited cancer cell metastasis and abolished the colony formation ability of cancer cells. Taken together, these results highlight that compound Xn-2 may be a promising theranostic TrxR inhibitor for human cancer therapy.