Synthesis and biological evaluation of novel artemisone-piperazine-tetronamide hybrids

For the first time, six novel artemisone-piperazine-tetronamide hybrids ( 12a-f ) were efficiently synthesised from dihydroartemisinin (DHA) and investigated for their in vitro cytotoxicity against some human cancer cells and benign cells. All the targets showed good cytotoxic activity in vitro . Hybrid 12a exhibited much better inhibitory activity against human liver cancer cell line SMMC-7721 (IC 50 = 0.03 ± 0.04 μM for 24 h) than the parent DHA (IC 50 > 0.7 μM), and two references, vincristine (VCR; IC 50 = 0.27 ± 0.03 μM) & cytosine arabinoside (ARA; IC 50 = 0.63 ± 0.04 μM). Furthermore, hybrid 12a had low toxicity against human benign liver cell line LO2 (IC 50 = 0.70 ± 0.02 μM for 24 h) compared with VCR, ARA, and DHA in vitro . Moreover, the inhibitory activity of hybrid 12a was obviously enhanced when human liver cancer cell line MHCC97H absorbed Fe 2+ in vitro . Six novel artemisone-piperazine-tetronamide hybrids were efficiently synthesised and investigated for their cytotoxicity against some human cancer cells.