biostudies-literatureWei MXNatural Science Foundation of Ningxia ProvinceNational Natural Science Foundation of ChinaNingxia University18333-18341https://www.ebi.ac.uk/biostudies/studies/S-EPMC9033422biostudies-literatureUnknown11(30)For the first time, six novel artemisone-piperazine-tetronamide hybrids (12a-f) were efficiently synthesised from dihydroartemisinin (DHA) and investigated for their <i>in vitro</i> cytotoxicity against some human cancer cells and benign cells. All the targets showed good cytotoxic activity <i>in vitro</i>. Hybrid 12a exhibited much better inhibitory activity against human liver cancer cell line SMMC-7721 (IC₅₀ = 0.03 ± 0.04 μM for 24 h) than the parent DHA (IC₅₀ > 0.7 μM), and two references, vincristine (VCR; IC₅₀ = 0.27 ± 0.03 μM) & cytosine arabinoside (ARA; IC₅₀ = 0.63 ± 0.04 μM). Furthermore, hybrid 12a had low toxicity against human benign liver cell line LO2 (IC₅₀ = 0.70 ± 0.02 μM for 24 h) compared with VCR, ARA, and DHA <i>in vitro</i>. Moreover, the inhibitory activity of hybrid 12a was obviously enhanced when human liver cancer cell line MHCC97H absorbed Fe²⁺ <i>in vitro</i>.RSC advancesSynthesis and biological evaluation of novel artemisone-piperazine-tetronamide hybrids.PMC9033422214620322021AAC050092019AAC03018G2020107490003Zhang SSLi XQYang JHHe YWei MXLiu XXYu JYYang PWZhang MWfalseSynthesis 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 <i>in vitro</i> cytotoxicity against some human cancer cells and benign cells. All the targets showed good cytotoxic activity <i>in vitro</i>. Hybrid 12a exhibited much better inhibitory activity against human liver cancer cell line SMMC-7721 (IC₅₀ = 0.03 ± 0.04 μM for 24 h) than the parent DHA (IC₅₀ > 0.7 μM), and two references, vincristine (VCR; IC₅₀ = 0.27 ± 0.03 μM) & cytosine arabinoside (ARA; IC₅₀ = 0.63 ± 0.04 μM). Furthermore, hybrid 12a had low toxicity against human benign liver cell line LO2 (IC₅₀ = 0.70 ± 0.02 μM for 24 h) compared with VCR, ARA, and DHA <i>in vitro</i>. Moreover, the inhibitory activity of hybrid 12a was obviously enhanced when human liver cancer cell line MHCC97H absorbed Fe²⁺ <i>in vitro</i>.2021-01-01T00:00:00Z2021 May2025-04-05T20:04:24.245Z2025-04-05T20:04:24.245ZS-EPMC90334223548092110.1039/d1ra00750e